共查询到20条相似文献，搜索用时 31 毫秒
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AIM To investigate the effect of bortezomib, a protease inhibitor, on the treatment of rheumatoid arthritis （RA） and it mechanism, based on interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. METHODS A total of 40 Wistar rats were randomly divided into 4 groups： control group, model group, and low- and high-dose bortezomib groups, with 10 rats in each group. In addition to control group, the rats in other groups were used to construct RA model. Bortezomib was given intraperitoneally at 0.2 mg/kg and 0.5 mg/kg in low- and high-dose bortezomib groups, respectively, while the rats in control group and model group were injected with the same amount of saline, once a day for 21 d. The general situation of the rats in each group was observed, the swelling degree of the foot was calculated, and the inflammation score was evaluated. HE staining was used to observe the pathological changes of ankle joint. The automatic biochemical analyzer was used to detect blood hemoglobin content, the total number of platelets （PLT）, serum creatinine （SCr） level and blood urea nitrogen （BUN） level. The serum levels of IL-6, tumor necrosis factor-α （TNF-α）, IL-33 and ST2 were measured by ELISA. The protein expression of IL-33 and ST2 in ankle tissues of each group was determined by Western blot. RESULTS On the 7th, 14th and 21th days after modeling, compared with control group, the degree of paw swelling in model group was significantly increased （P <0.05）. Compared with model group, the swelling degree of paw in low- and high-dose groups was decreased （P <0.05）. At the end of administration, compared with control group, the synovial cells in model group were increased and in disorder, with a lot of inflammatory exudates in the articular cavity, and the inflammatory score, the levels of PLT, SCr and BUN, the serum levels of IL-6, TNF-α, IL-33 and ST2, and the protein expression of IL-33 and ST2 in ankle tissues were significantly increased （P <0.05）. Compared with model group, the inflammatory exudates in the articular cavity of the rats in low- and high-dose bortezomib groups were decreased, and the inflammatory score, the levels of PLT, SCr and BUN, the serum levels of IL-6, TNF-α, IL-33 and ST2, and the protein expression of IL-33 and ST2 in ankle tissues were decreased （P <0.05）. CONCLUSION Bortezomib may reduce the inflammation and swelling of the joints in RA rats by regulating the IL-33/ST2 signaling pathway. 相似文献
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GUO Wan-rong CHEN Zong-lan CAO Huan-yi DENG Hong-rong CAI Meng-yin LIANG Hua XU Fen 《园艺学报》2000,36(11):1921-1927
AIM To investigate the alleviating effect of exenatide （Exe）, a glucagon-like peptide-1 （GLP-1） receptor agonist, on the ectopic lipid accumulation in skeletal muscle of ob /ob mice and its mechanism. METHODS Eight-week-old male ob /ob mice and their wild-type （WT） littermates were randomly divided into 3 groups, ob /ob group, ob /ob +Exe group and WT group, and treated with Exe at 24 nmol/kg or the same volume of saline intraperitoneally once daily for 4 weeks. The body weight, fasting blood glucose （FBG） and fat content were measured after the 4-week treatment. The oil red O staining and the quantification of triglyceride （TG） were performed on the skeletal muscle. The serum levels of TG, total cholesterol and free fatty acid （FFA） were also measured by ELISA. The expression levels of AMP-activated protein kinase （AMPK） and lipid metabolism-related proteins were determined by Western blot. Mouse myoblast C2C12 cells were used as an in vitro model to further investigate the effects of Exe. RESULTS As compared with the ob /ob mice treated with saline, 4-week Exe treatment did not reduce body weight, FBG, food intake and fat content in ob /ob mice （P >0.05）. However, serum FFA was decreased （P <0.05）. Oil red O staining and the quantification of TG showed that 4-week Exe treatment significantly attenuated the ectopic lipid accumulation in the skeletal muscle of ob /ob mice （P <0.05）. The results of Western blot showed that the levels of phosphorylated AMPK （p-AMPK） and lipolysis-related proteins were up-regulated, while the lipid synthesis-related proteins were down-regulated by Exe （P <0.05）. Treatment with Exe alleviated the lipid accumulation in the C2C12 cells induced by sodium palmate （P <0.05）, and the effects of Exe on the levels of p-AMPK and lipid metabolism-related proteins in the C2C12 cells were consistent with those in the ob /ob mice （P <0.05）. Treatment with Exe also up-regulated the protein expression of glucose transporter 4 and improved the ability of glucose uptake in the C2C12 cells （P <0.05）. CONCLUSION Short-term Exe treatment attenuates the ectopic lipid accumulation in skeletal muscle of ob /ob mice by up-regulating lipolysis-related proteins and down-regulating lipid synthesis-related proteins, which is independent on body weight loss. 相似文献
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AIM To investigate the effects of Triptergium wilfordii multiglucoside （TWM） on intestinal flora and immune function in IgA nephropathy （IgAN） rats based on core 1 β1,3-galactosyltransferase （C1GALT1） and its chaperone protein Cosmc （C1GALT1/Cosmc pathway）. METHODS The rat model of IgAN was established, and the animals were randomly divided into model group （IgAN group）, dexamethasone （Dex） group and TWM group. Normal rats served as normal control （NC） group. The levels of serum creatinine （SCr） and blood urea nitrogen （BUN）, 24-hour urinary total protein （24 h UTP） and the number of urinary red blood cells were measured by automatic biochemical analyzer. The levels of serum IgA1, and plasma tumor necrosis factor-α （TNF-α）, B-cell activating factor （Baff） and interleukin-17 （IL-17） were detected by ELISA. The level of galactose-deficient IgA1 （Gd-IgA1） was detected by Vicia villosa lectin affinity ELISA. The intestinal colony was cultured in selective bacterial medium. The ratio of CD4+ CD25+ regulatory T cells （Treg） to CD4+ T cells （Treg proportion） in peripheral blood mononuclear cells （PBMC） was detected by flow cytometry.Western blot was used to determine the protein expression of C1GALT1 and Cosmc in intestinal mucosa. RESULTS Compared with NC group, 24 h UTP, the number of urinary red blood cells, SCr, BUN, serum IgA1 and Gd-IgA1, the numbers of Enterobacteriaceae , Enterococcus and Bacteroides , and the levels of TNF-α, Baff and IL-17 in plasma in IgAN group were significantly increased （P <0.05）, while the numbers of Bifidobacteria and Lactobacilli , the Treg proportion in PBMC, and the protein expression levels of C1GALT1 and Cosmc in intestinal mucosa were significantly decreased （P <0.05）. Compared with IgAN group, 24 h UTP, the number of urinary red blood cells, SCr, BUN, serum IgA1 and Gd-IgA1, the numbers of Enterobacteriaceae , Enterococcus and Bacteroides , and the levels of TNF-α, Baff and IL-17 in plasma in Dex group and TWM group were significantly reduced （P <0.05）, and those in TWM group were lower than those in Dex group （P <0.05）. Moreover, the numbers of Bifidobacteria and Lactobacilli , the Treg proportion in PBMC, and the protein expression levels of C1GALT1 and Cosmc in intestinal mucosa were significantly elevated （P <0.05）, and those in TWM group were higher than those in Dex group （P <0.05）. CONCLUSION TWM reduces the abnormal glycosylation level of IgA in IgAN rats by promoting the activation of C1GALT1/Cosmc pathway, and attenuates the intestinal flora disorder and immune dysfunction in IgAN rats, thus exerting the therapeutic effect. 相似文献
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AIM To investigate the effects of astragaloside on the levels of sex hormone and oxidative stress in rats with polycystic ovary syndrome （PCOS）. METHODS Female SD rats （n =60） were randomly divided into normal control group, model group, Diane-35 （0.339 2 mg/kg） group, low dose astragaloside （12.5 mg/kg） group and high dose astragaloside （50 mg/kg） group, with 12 rats in each group. The PCOS model was induced by letrozole （1 mg/kg）, which was administered by gavage once a day for 3 weeks. After administration, the estrus cycle of the rats was observed by vaginal smear, and the ovarian index was calculated. HE staining was used to observe the histopathological changes of the ovaries. Serum levels of the sex hormones testosterone （T）, estradiol （E2）, luteinizing hormone （LH） and follicle-stimulating hormone （FSH） were measured by ELISA. The levels of superoxide dismutase （SOD）, malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） in serum and ovarian tissue were detected by colorimetry, and the protein levels of steroidogenetic acute regulatory protein （StAR） and apoptosis-related proteins cleaved caspase-3, Bax and Bcl-2 in ovarian tissue were detected by Western blot. RESULT Compared with control group, the oestrous cycle of the rats in model group was disorder, and the ovarian index was increased, ovary was polycystic. The serum levels of T, LH and MDAwere significantly increased （P <0.05）, while the contents of E2, FSH and the activities of GSH-Px and SOD were significantly decreased （P <0.05）. The levels of MDA, StAR, cleaved caspase-3 and Bax proteins in ovarian tissue were significantly up-regulated （P <0.05）. GSH-Px and SOD activities and Bcl-2 protein levels were significantly down-regulated （P <0.05）. CONCLUSION Astragalosideeffectively balances the levels of sex hormone in PCOS rats and relieves the oxidative stress injury, the mechanism may be related to the inhibition of StAR expression. 相似文献
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AIM To investigate the effects of geniposide （Gen） on Toll like receptor 4/nuclear factor-κB （TLR4/NF-κB） signaling pathway and cognitive dysfunction in sleep deprived rats. METHODS Wistar rats （n =120） were randomly divided into normal control （NC） group, model （M） group, low-dose （5 g·kg-1·d-1） Gen （Gen-L） group, medium-dose （10 g·kg-1·d-1） Gen （Gen-M） group, high-dose （20 g·kg-1·d-1） Gen （Gen-H） group and Gen-H+LPS （0.4 mg·kg-1·d-1, tail vein injection） group. After 7 days of intervention, the sleep deprivation model of rats in M group, Gen-L, Gen-M, Gen-H and Gen-H+LPS group was established by improved small platform water environment. The escape latency of Morris water maze experiment and the behavior correct rate of Y maze experiment were measured. The serum levels of S100B and neuron-specific enolase （NSE）, and the levels of interleukin-1β （IL-1β）, IL-6 and tumor necrosis factor-α （TNF-α） in hippocampus were detected by ELISA. The mRNA levels of TLR4 and NF-κB p65 were detected by RT-qPCR, and the protein levels of TLR4 and NF-κB p65 were determined by Western blot. RESULTS Compared with NC group, the escape latency, the serum levels of S100B and NSE, the hippocampal levels of IL-1β, IL-6 and TNF-α, and the mRNA and protein expression of TLR4 and NF-κB p65 were increased significantly in M group （P <0.01）, and the behavior correct rate was decreased significantly （P <0.01）. Compared with M group, the escape latency, the hippocampal levels of IL-1β, IL-6 and TNF-α, and the expression of TLR4 and NF-κB p65 at mRNA and protein levels were decreased significantly in Gen-L, Gen-M and Gen-H groups （P <0.01）, and the behavior correct rate was increased in turn （P <0.01）. Compared with Gen-H group, the escape latency, the serum levels of S100B and NSE, the hippocampal levels of IL-1β, IL-6 and TNF-α, and the expression of TLR4 and NF-κB p65 at mRNA and protein levels were increased significantly in Gen-H+LPS group （P <0.01）, and the behavior correct rate was decreased significantly （P <0.01）. CONCLUSION Geniposide may inhibit the TLR4/NF-κB p65 signaling pathway to effectively improve cognitive function in sleep-deprived rats and reduce hippocampus inflammation. 相似文献
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AIM To investigate the association between soluble phospholipase A2-X（sPLA2-X） and eosinophils in bronchial asthma, and to provide new insight and strategies for the treatment of bronchial asthma. METHODS Female Babl/c mice （n =48） of SPF grade and 6~8 weeks old were divided into 4 groups （with 12 in each group： healthy control group,asthma control group, eosinophil deletion group, and asthma /eosinophil deletion isotype control group）. The mouse model of bronchial asthma was constructed. The mice in healthy control group were intraperitoneally injected with saline on days 0, 7, and 14. The mice in other groups were intraperitoneally injected with 50 μg OVA and 2 mg aluminum hydroxide gel（soluble in 200 μL saline.On the 21st d and 26 th d, eosinophil deletion antibody （anti-CCR3） and isotype control were intraperitoneally injected and intranasally respectively, and then the lungs function test was conducted within 48 h after the end of nebulization.Half of the mice in each group were subjected to whole lung lavage, the remaining half were used for lung tissue section with HE staining, the whole blood was used to measure serum IgE, the supernatant of broncho alveolar lavage fluid （BALF） was used to measure cytokines, and total number of cells in the bronchoalveolar lavage fluid was analyzed for cell classification and flow cytometry. RESULTS （1）Compared with asthma control group,the airway and alveolar inflammatory responses in asthma/eosinophil deletion group was significantly alleviated.（2） Compared with asthma control group, anti-CCR3 successfully deleted eosinophils, and the percentage of eosinophils in bronchoalveolar lavage fluid in asthma/eosinophil deletion group was significantly reduced （P <0.05）.（3） The airway hyperresponsiveness in asthma/eosinophil deletion group was significantly decreased as compared with asthma control group（P <0.05）.（4） The levels of sPLA2-X in the serum and BALF was significantly reduced in asthma/eosinophil deletion group as compared with asthma control group（P <0.05）.（5）Compared with asthma control group,the levels of IL-4, IL-5, and IL-13 in the BALF of the mice in asthma/eosinophil deletion group were significantly reduced, and the serum level of IgE was also decreased （P <0.05）. CONCLUSION Eosinophils in bronchial asthma are importantly associated with sPLA2-X. 相似文献
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AIM To explore the anti-atherosclerotic mechanism of Wendan decoction based on reverse cholesterol transport. METHODS Eight-week-old apolipoprotein E gene knockout （ApoE -/-） mice with high-fat diet and daily drug gavage were randomly divided into model group, simvastatin group, and low-, middle- and high-dose Wendan decoction groups, with 15 mice in each group. The C57BL/6 mice of the same age served as control group. The mice were weighed once every week. After 10 weeks, the mice were anesthetized with chloral hydrate. The serum were collected for lipid level examination. The atherosclerotic plaque buildup in aortic root and whole aorta was observed by HE staining and oil red O staining, respectively. The levels of proteins related to cholesterol transport, ATP-binding cassette transporter A1 （ABCA1） and caveolin-1 in the aorta, and scavenger receptor class B type I （SR-BI） and CD36 in the liver, were quantified by Western blot. RESULTS Wendan decoction at middle dose inhibited the increase in the body weight of ApoE -/- mice fed with high-fat diet （P <0.05）. Wendan decoction at different doses significantly reduced the serum levels of triglyceride, total cholesterol and low-density lipoprotein cholesterol in the ApoE -/- mice （P <0.05 or P <0.01）, but had no effect on serum high-density lipoprotein cholesterol level （P >0.05）. Wendan decoction at different doses inhibited the formation of atherosclerotic plaques in whole aorta of the ApoE -/- mice （P <0.05 or P <0.01）. Middle- and high-dose Wendan decoction significantly inhibited the formation of atherosclerotic plaques in the aortic root （P <0.05）. Bedsides, Wendan decoction at different doses increased the protein level of ABCA1 and decreased the protein level of caveolin-1 in the aorta of the ApoE -/- mice （P <0.01）. Middle- and high-dose Wendan decoction increased the liver protein level of SR-BI in the ApoE -/- mice （P <0.01）. However, Wendan decoction at different doses had no effect on the liver protein level of CD36 in the ApoE -/- mice （P >0.05）. CONCLUSION Wendan decoction reduces the body weight, serum lipid levels and formation of atherosclerotic plaques in ApoE -/- mice fed with high-fat diet, and its mechanism is related to up-regulation of ABCA1 protein level in the aorta and SR-BI protein level in the liver as well as down-regulation of caveolin-1 protein level in the aorta. 相似文献
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Destruction of autophagy marker LC3 rhythm is involved in β1-AA-induced H9c2 rat cardiomyocyte death
JIA Wei-wei NING Na SUN Cong LI Peng-jia LU Jie-bei ZHANG Sheng YUAN Yuan WANG Li WANG Xiao-hui 《园艺学报》2021,37(1):10-17
AIM To investigate the effect of β1-adrenergic receptor autoantibodies （β1-AA） on the rhythm of autophagy marker microtubule-associated protein 1 light chain 3 （LC3）, and the underlying mechanism of cardiomyocyte death. METHODS The test materials were Sprague-Dawley （SD） rats and H9c2 rat cardiomyocytes. The SD rats were randomly divided into immunization group and control group with 6 rats in each group. The H9c2 cells were randomly divided into control group, β1-AA group, lentivirus （LV）-NC group, and LV-shPer2 group （n =6）. Affinity chromatography was used for purification of β1-AA from rat serum. CCK-8 assay was used to observe the viability of cardiomyocytes treated with β1-AA for 24 h. The cells were synchronized by dexamethasone and then treated with β1-AA. The mRNA and protein levels of LC3 at different time points were determined by real-time PCR and Western blot, respectively. The Per2 protein level at different time points was also determined by by Western blot. JTK_CYCLE algorithm was used to estimate the circadian rhythm parameters. After destruction of LC3 circadian rhythm via LV-shPer2, CCK-8 assay was used to measure the viability of H9c2 cells. RESULTS High level of β1-AA in rat serum was found after active immunization compared with control group （P <0.05）. The viability of H9c2 cells in β1-AA group was significantly lower than that in control group （P <0.05）. The LC3 and Per2 rhythms were both disrupted in H9c2 cells induced by β1-AA （JTK_CYCLE P <0.05）. After LV-shPer2 infection, the LC3 rhythm was disrupted （JTK_CYCLE P <0.05） and the cell viability was reduced （P <0.05）. CONCLUSION β1-AA may induce the destruction of autophagy marker LC3 rhythm in rat cardiomyocytes and then promote cell death. 相似文献
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Role and potential mechanism of fecal microbiota transplantation in treatment of chronic hepatitis B
WEI Qi YANG Jing-nan HE Xue-liang HE Qiao-ling SI Hui-fang HU Hong BAI Chun-yang WANG Hui-chao LIN Xu-hong 《园艺学报》2000,36(10):1833-1843
AIM To investigate the effect of fecal microbiota transplantation （FMT） on the treatment of chronic hepatitis B （CHB） and the potential mechanism. METHODS Fifty C57BL/6J mice （6~8 weeks old） were divided into 5 groups： control group, CHB group, entecavir （ETV） group, comprehensive treatment （ETV+FMT, EFMT） group, and blocker （TAK-242+ETV+FMT, EFMT-TAK） group. The mice in each group were given corresponding treatment. The general condition of the mice was observed daily, and fecal specimens were kept every 10 d. The mice were sacrificed after 12 weeks, and the liver tissues and blood samples were collected. HE staining was used for histological scoring. Serum hepatitis B surface antigen （HBsAg） and interleukin-18 （IL-18） levels were measured by ELISA. Toll-like receptor 4 （TLR4） expression was detected by flow cytometry. Intestinal flora diversity was analyzed by high-throughput sequencing. RESULTS （1） Compared with control group, the body weight of the mice in CHB group was significantly reduced （P <0.05）. The body weight loss of the mice in ETV group, EFMT group and EFMT-TAK group was reversed to some extent as compared with CHB group （P <0.05）. （2） The histological score of the mice in CHB group was significantly higher than that in control group （P <0.05）. The score in ETV group was lower than that in CHB group （P <0.05）. The scores in EFMT group and EFMT-TAK group were lower than that in ETV group （P <0.05）, and that in EFMT-TAK group had a further downward trend compared with EFMT group （P <0.05）. （3） Compared with control group, the serum level of HBsAg in the CHB mice was significantly increased （P <0.05） and decreased after ETV treatment （P <0.05）. The HBsAg level in both EFMT group and EFMT-TAK group was significantly lower than that in ETV group （P <0.05）. （4） The IL-18 level in CHB group was significantly higher than that in control group （P <0.05）. After ETV treatment, the IL-18 level was decreased （P <0.05）, and that in both EFMT group and EFMT-TAK group was decreased more than that in ETV group （P <0.05）. （5） TLR4 expression in CHB group was higher than that in control group （P <0.05）, that in ETV group was lower than CHB group （P <0.05）, and that in EFMT group was further decreased （P <0.05）. （6） The heat map analysis at the class level showed that the abundances of Gammaproteobacteria , Deltaproteobacteria and Negativicutes in CHB group were significantly higher than those in control group, and those of Deltaproteobacteria and Negativicutes in EFMT group were close to those in control group. The heat map analysis at the family level indicated that the abundances of Burkholderiaceae , Desulfovibrionaceae and Veillonellaceae in CHB group were significantly higher than those in control group, while those in ETV group and EFMT group gradually approached normal levels. The α diversity index in CHB group was significantly decreased, while the diversity in ETV group was increased, that in EFMT group was further increased, and that in EFMT-TAK group was the highest. CONCLUSION FMT plays an active role in the treatment of CHB. The mechanism may be related to reducing the level of IL-18 and improving the structure and diversity of intestinal flora. The TLR4 signaling pathway is involved. 相似文献
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LIU Cai-hong ZHANG Yan-wei LIU Wei-xia GUO Rui MENG Zhi-jun GAO Jia Wang Jing WANG Ya-jing 《园艺学报》2000,36(8):1470-1475
AIM To investigate the relationship between the serum levels of C1q/TNF-related protein (CTRP) 1 and CTRP7 and coronary atherosclerotic heart disease (CAD) in the patients with or without type 2 diabetes mellitus (T2DM). METHODS Totally 138 cases of participants were selected, and divided into control group (without T2DM or CAD; n =40), T2DM group (with T2DM, but without CAD; n =30), CAD group (with CAD, but without T2DM; n =40), and CAD+T2DM group (with both T2DM and CAD; n =28). The serum levels of CTRP1 and CTRP7 in these participants were measured by ELISA. RESULTS (1) Compared with control group, serum CTRP1 level in CAD group and CAD+T2DM group was significantly increased (P <0.05 or P <0.01), and serum CTRP7 level in CAD, T2DM and CAD+T2DM groups was significantly decreased (P <0.05 or P <0.01). (2) Increased serum CTRP1 level was a risk factor for CAD [odds ratio (OR)=1.136; 95% confidence interval (CI): 1.010~1.278; P =0.034). Sex, hypertension and serum triglyceride level were also correlated with CAD. Decreased serum CTRP7 level was a risk factor for T2DM (OR=0.984; 95% CI: 0.969~0.999; P =0.038). Sex, hypertension and serum high-density lipoprotein cholesterol level were also correlated with T2DM. Increased serum CTRP1 level was a risk factor for CAD+T2DM (OR=1.009; 95% CI: 1.005~1.203; P =0.040). Hypertension was also a risk factor for CAD+T2DM. (3) In CAD group, serum CTRP1 level had certain diagnostic value, and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.670 (95% CI: 0.580~0.760; P =0.001), but serum CTRP7 level had no diagnostic value for CAD. In T2DM group, both serum CTRP1 and CTRP7 levels had diagnostic value, and the AUC values of their ROC curves were 0.607 (95% CI: 0.505~0.710; P =0.032) and 0.665 (95% CI: 0.574~0.756; P =0.001), respectively. In CAD+T2DM group, both serum CTRP1 and CTRP7 levels had diagnostic value, and the AUC values of their ROC curves were 0.666 (95% CI: 0.552~0.781; P =0.007) and 0.632 (95% CI 0.517~0.747; P =0.032), respectively. CONCLUSION Increased serum CTRP1 level and decreased serum CTRP7 level are associated with increased risk of T2DM and CAD. Increased serum CTRP1 level is a risk factor for CAD and CAD+T2DM, while decreased serum CTRP7 level is a risk factor for T2DM. Serum CTRP1 level has certain specificity and sensitivity for the diagnosis of CAD, T2DM and CAD+T2DM, while serum level of CTRP7 has certain specificity and sensitivity for the diagnosis of T2DM and CAD+T2DM. 相似文献
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AIM To study whether C1q/tumor necrosis factor （TNF）-related protein 3 （CTRP3）protect vascular endothelium in rats with hyperuricemia and its potential mechanisms. METHODS An animal model of hyperuricemia was established by using male SD rats drinking 10% fructose water （n =10）. The rats drinking normal water served as normal controls （n =10）. After 12 weeks, the rats were given a single injection with Ad-CTRP3 or Ad-GFP. The experiment was ended at 14th day after transfection.The serum levels of uric acid and nitric oxide （NO） were evaluated. The serum contents of TNF-α and interleukin-6 （IL-6） were measured by ELISA. HE staining and TUNEL assay were used to assess the morphological changes of intima and apoptosis of endothelial cells in thoracic aorta, respectively. The mRNA levels of endothelial nitric oxide synthase （eNOS）, TNF-α and IL-6 were detected by RT-qPCR. The protein levels of CTRP3 and Toll-like receptor 4 （TLR4） were determined by Western blot. RESULTS Compared with normal control group, the rats with hyperuricemia showed lower CTRP3 and higher TLR4 protein levels in the thoracic aorta （P <0.05）. Hyperuricemic rats had higher serum contents of uric acid, TNF-α and IL-6 （P <0.05）. Also, the intima structure disturbance of thoracic aorta, increased apoptotic rate, higher mRNA levels of TNF-α and IL-6 as well as lower mRNA levels of eNOS were observed （P <0.05）. By contrast, CTRP3 over-expression decreased TLR4 protein levels, reduced inflammatory cytokines, and obviously improved the morphology and function of thoracic aorta in the rats with hyperuricemia. CONCLUSION CTRP3 protect vascular endothelium in rats with hyperuricemia maybe via down-regulation of TLR4- mediated inflammatory signaling pathway. 相似文献
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AIM To investigate the effects of curcumin （Cur） on the inflammatory response of human gingival fibroblasts （HGFs） induced by Porphyromonas gingivalis （Pg） lipopolysaccharide （LPS） and the role of microRNA-124 （miR-124） in this process. METHODS The HGFs were divided into control group, LPS group （10 mg/L LPS） and LPS+Cur （20, 40 and 80 μmol/L） groups （10 mg/L LPS+corresponding dose of Cur）. After treatment for 24 h, CCK-8 assay was used to measure the cell viability. ELISA was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the supernatant. The level of miR-124 in the cells was detected by RT-qPCR. The protein levels of nuclear factor kappa B （NF-κB） p-p65 in cytoplasm and nucleus were determined by Western blot, and the nuclear translocation of NF-κB p-p65 was evaluated by laser confocal microscopy. After transfection with mimic-NC or miR-124 mimic, the expression of miR-124 and NF-κB p-p65 protein in the cytoplasm and nucleus of the cells were also detected. RESULTS The cell viability, the level of miR-124 in the cells and NF-κB p-p65 protein level in cytoplasm of LPS group were lower than those in control group （P <0.05）, while the levels of IL-1β and TNF-α in the supernatant and NF-κB p-p65 protein level in the nucleus were higher than those in control group （P <0.05）. The cell viability, the level of miR-124 in cells and NF-κB p-p65 protein level in the cytoplasm of LPS+Cur （40 and 80 μmol/L） groups were higher than those in LPS group （P <0.05）, while the level of TNF-α in the supernatant and NF-κB p-p65 protein level in the nucleus were lower than those in LPS group （P <0.05）. The level of IL-1β in the supernatant of LPS+80 μmol/L Cur group was lower than that in LPS group （P <0.05）. The levels of miR-124 and NF-κB p-p65 protein level in the cytoplasm of miR-124 mimic group were higher than those in LPS group and mimic-NC group （P <0.05）, while the level of NF-κB p-p65 proteinlevel in the nucleus was lower than that in LPS group and mimic-NC group （P <0.05）. CONCLUSION Curcumin inhibits the inflammatory response of HGFs induced by Pg LPS, which may be achieved by up-regulating miR-124 and then inhibiting the nuclear translocation of NF-κB p-p65. 相似文献
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ZHAO Jun-lin ZHANG Ying-ying DUAN Ling-di ZHAO Si-qi RUAN Yuan-yuan PENG Can ZHANG Fan GUO Bing 《园艺学报》2020,36(5):893-898
AIMTo observe the effect of resveratrol (Res) on renal autophagy level and renal interstitial fibrosis in the mice with diabetes mellitus (DM), and to discuss the possible mechanism. METHODSThe wild-type C57BL/6 mice were randomly divided into 3 groups, including normal control (NC) group, DM group and Res group (8 in each group). The diabetic mouse model was established by injection of streptozotocin. After 8 weeks of successful replication of the diabetic model, Res was given to the mice in Res group by continuous gavage for 12 weeks, and then the mice in each group were sacrificed to detect the relevant biochemical parameters. The pathological changes of the kidney tissues were observed by HE staining and Masson staining. The levels of the proteins related to autophagy, epithelial-mesenchymal transition (EMT) and fibrosis were determined by Western blot. The mRNA expression of collagen type IV (Col IV), α-smooth muscle actin (α-SMA) and E-cadherin were detected by real-time PCR. RESULTSCompared with NC group, fasting blood glucose (FBG), kidney index (KI), serum creatinine, 24-hour urinary albumin excretion rate and 24-hour urine total protein were remarkably increased in DM group (P <0.05). The results of HE and Masson staining indicated that renal tissue presented fibrosis in DM group. The protein levels of E-cadherin, beclin-1, microtubule-associated protein 1 light chain 3-II (LC3-II) were reduced in DM group, while the levels of α-SMA, Col IV and Snail1 were increased (P <0.05). After intervention with Res for 12 weeks, all the relevant biochemical parameters and KI were reduced (P <0.05) except FBG (P >0.05), and renal fibrosis lesions were obviously alleviated. Compared with DM group, the protein levels of E-cadherin, beclin-1 and LC3-II were increased in Res group, but the protein expression levels of α-SMA, Col IV, Snail1 were reduced (P <0.05). Compared with DM group, the mRNA level of E-cadherin was increased in Res group , but the mRNA levels of Col IV and α-SMA were reduced (P <0.05). CONCLUSION Resveratrol significantly inhibits EMT and reduces renal interstitial fibrosis in diabetic mice, and its mechanism may be related to the promotion of renal autophagy. 相似文献
16.
AIM To analyze the regulatory effect of quercetin （QUE） on PTEN-induced putative kinase 1 （PINK1）/parkin mitochondrial autophagy pathway, and to explore the mechanism of quercetin in relieving cerebral ischemia/reperfusion （I/R） injury. METHODS Sixty SD male rats were randomly divided into sham operation group, model group （I/R group）, QUE group,3-methyladenine （3-MA） group and QUE+3-MA group. Administration started in each group 3 days before modeling, once a day, at 30 min after the last administration,except sham group, the other groups used 4-vessel blockage method to establish the whole brain I/R model. On the day after modeling, the neural function was evaluated by neuropathy disability score （NDS）. The volume of cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride （TTC） staining. The morphological changes of mitochondria in hippocampus were observed by transmission electron microscopy. The contents of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in hippocampus were measured by ELISA. The activity of superoxide dismutase （SOD） and contents of malondialdehyde （MDA） in hippocampus were detected by xanthine oxidase method, thiobarbituric acid condensation method. Western blot was used to detect the proteinex pression of PINK1, parkin and LC3-II in brain tissue. RESULTS Compared with sham group, the hippocampus of the rats in I/R group and QUE+3-MA group showed swelling of mitochondria, destruction or disappearance of internal crista and other pathological damage,also the volume of cerebral infarction, the contents of IL-6, TNF-α and MDA, the protein expression levels of PINK1, parkin and LC3-II were increased （P <0.05）, while NDS score and activity of SOD were decreased （P <0.05）. Compared with I/R group and QUE+3-MA group, the pathological damage degree of hippocampus in QUE group was reduced, the volume of cerebral infarction, the contents of IL-6, TNF-α and MDA were decreased （P <0.05）, the proteinexpression levels of PINK1, parkin and LC3-II, and NDS score and activity of SOD were increased （P <0.05）.The above indexes in 3-MA group were opposite to QUE group. No significant difference in the above indexes between I/R group and QUE+3-MA group was observed （P >0.05）. CONCLUSION Quercetin activates mitochondrial autophagy and reduces cerebral I/R by regulating the expression of PINK1/parkin pathway proteins. 相似文献
17.
AIM To investigate the mechanism of long noncoding RNA （lncRNA） FEZF1-AS1 regulating microRNA-363-3p （miR-363-3p） on the viability and apoptosis of lipopolysaocharide （LPS）-induced vascular endothelial cells. METHODS Human umbilical vein endothelial cells （HUVECs） were cultured in vitro . pcDNA-NC, pcDNA-FEZF1-AS1, anti-miR-NC, anti-miR-363-3p, miR-NC and miR-363-3p mimics were transfected into the HUVECs and LPS stimulation was applied for 24 h. RT-qPCR was used to detect the expression of FEZF1-AS1 and miR-363-3p. The cell viability was measured by MTT assay. The apoptotic rate was analyzed by flow cytometry. The dual-luciferase reporter experiment was used to verify the targeted regulation of FEZF1-AS1 and miR-363-3p. Western blot was used to determined the expression of cyclin D1, Ki67 and cleaved caspase-3. RESULTS Compared with control group, the expression level of FEZF1-AS1 in LPS group was significantly reduced （P <0.05）, and the expression level of miR-363-3p was significantly increased （P <0.05）. Compared with pcDNA-NC+LPS group, the cell viability in pcDNA-FEZF1-AS1+LPS group was significantly increased （P <0.05）, the apoptotic rate was significantly reduced （P <0.05）, the protein levels of cyclin D1 and Ki67 were significantly increased （P <0.05）, and the protein level of cleaved caspase-3 was significantly reduced （P <0.05）. Compared with anti-miR-NC+LPS group, the cell viability in anti-miR-363-3p+LPS group was significantly increased （P <0.05）, the apoptotic rate was significantly reduced （P <0.05）, the protein levels of cyclin D1 and Ki67 were significantly increased （P <0.05）, and the protein level of cleaved caspase-3 was significantly reduced （P <0.05）. Dual-luciferase reporter experiment confirmed that FEZF1-AS1 targeted miR-363-3p. Compared with miR-NC+pcDNA-FEZF1-AS1+LPS group, the cell viability in miR-363-3p+pcDNA-FEZF1-AS1+LPS group was significantly reduced （P <0.05）, the apoptotic rate was significantly increased （P <0.05）, the protein levels of cyclin D1 and Ki67 were significantly reduced （P <0.05）, and the protein level of cleaved caspase-3 was significantly increased （P <0.05）. CONCLUSION Over-expression of FEZF1-AS1 promotes the viability and inhibits apoptosis of LPS induced vascular endothelial cells by inhibiting the expression of miR-363-3p. 相似文献
18.
AIM To explore the anti-atherosclerotic mechanism of Wendan decoction based on formation of foam cells. METHODS The optimal concentrations of Wendan decoction without cytotoxity to cells were selected by MTT assay. After Wendan decoction treatment, the formation of foam cells was examined by oil red O staining. The cholesterol efflux, cholesterol level, free cholesterol level and cholesterol esterification rate were analyzed using cholesterol efflux assay, total cholesterol assay and free cholesterol assay. The expression levels of macrophage membrane proteins, including CD36, scavenger receptor class A （SR-A）, ATP-binding cassette transporter A1 （ABCA1） and scavenger receptor class B type I （SR-BI）, were quantified by Western blot. RESULTS The optimal concentrations of Wendan decoction without cytotoxity to the cells were 0~6 g/L. Wendan decoction at the concentrations of 1.5, 3 and 6 g/L were selected for the experiments. Wendan decoction at these concentrations inhibited the formation of foam cells induced by oxidized low-density lipoprotein （ox-LDL）, and reduced the accumulation of intracellular lipids in a concentration-dependent manner （P <0.05 or P <0.01）. Wendan decoction also reduced intracellular total cholesterol level, cholesterol ester level and cholesterol esterification rate （P <0.05 or P <0.01）, promoted efflux of intracellular cholesterol （P <0.01）, and decreased the protein level of CD36 in THP-1 cell-derived macrophages （P <0.01） in a concentration-dependent manner. Wendan decoction at the concentration of 6 g/L significantly reduced the protein level of SR-A in THP-1 cell-derived macrophages （P <0.05）. At the concentrations of 3 and 6 g/L, Wendan decoction significantly increased the protein levels of ABCA1 and SR-BI in THP-1 cell-derived macrophages （P <0.05 or P <0.01）. CONCLUSION Wendan decoction significantly inhibits ox-LDL-induced formation of foam cells by reducing cholesterol deposition and promoting cholesterol efflux, and its mechanism may be related to the down-regulation of CD36 and SR-A and the up-regulation of ABCA1 and SR-BI. 相似文献
19.
QIAN Wei LOU Guo-qiang ZHOU Zhuo-lin WANG Jia LIU Xiu-jie HAO Mao-lin WANG Wan-tie 《园艺学报》2000,36(11):2056-2061
AIM To investigate the role of curcumin （CUR） in lung ischemia/reperfusion （I/R） injury （LIRI） and its relationship with autophagy. METHODS 40 SD rats were randomly divided into sham operation （sham） group, I/R group, solvent （DMSO） group, CUR group and CUR+rapamycin （CUR-Rap） group. The rats were intraperitoneally injected with normal saline, DMSO, CUR or CUR+Rap before operation. After the rat LIRI model was established, the lung tissues were taken to measure W/D, TLW, IAR, and the contents of SOD and MDA were also measured to indicate the oxidative stress level. Light and electron microscopes were used to observed the morphology and ultrastrucure of lung tissues. The expression levels of autophagy-related proteins were determined by Western blot to evaluate autophagy levels. RESULTS Compared with sham group, wet weight/dry weight （W/D）, total lung water （TLW）, injured alveoli rate（IAR） and malondialdehyde （MDA） content in all other groups were increased, superoxide dismutase （SOD） activity was decreased, the levels of autophagy were increased （P <0.05）, and lung tissue injury and cell ultrastructural damage were aggravated in CUR group. Compared with DMSO group, W/D, TLW and IAR and MDA content were decreased, SOD activity was decreased, autophagy levels were also decreased （P <0.05）, and lung tissue and cell ultrastructural damage were attenuated. Compared with CUR group, W/D, TLW, IAR and MDA content were increased, SOD activity declined, the autophagy levels were increased （P <0.05）, and damage of lung tissues and cells were more serious in CUR-Rap group. CONCLUSION Curcumin attenuates the lung I/R injury in rats, and its mechanism may be related to the reduction of oxidative stress and the inhibition of autophagy. 相似文献
20.
XU Jia-qi AN Mei-ling YUAN Yue HAO Yi-fan WANG Xiu-wen ZHANG Min WEI Xiao-wei LI Hua WANG Ren-jun 《园艺学报》2021,36(12):2148-2158
AIM To investigate whether microRNA-9-5p （miR-9-5p） mediates sympathetic overactivity by targeting KCNN3 （potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3） gene,which encoded small-conductance calcium-activated potassium channel 3 （SK3） protein, in paraventricular nucleus （PVN） of rats with type 2 diabetes mellitus （T2D）. METHODS A rat model of T2D was established by high-fat diet combined with intraperitoneal injection of 30 mg/kg streptozotocin. The levels of miR-9-5p and KCNN3 mRNA in PVN were detected by real-time PCR. The relationship between KCNN3 and miR-9-5p was predicted by TargetScan. Recombinant adeno-associated virus （rAAV）-miR-9-5p or KCNN3 were bilaterally microinjected into the PVN to observe the changes in plasma glucose levels and sympathetic drive indicators. The number of FosB and SK3 positive cells was measured by immunofluorescence staining. The protein expression of SK3 was determined by Western blot. The relationship between KCNN3 and miR-9-5p were confirmed by cell transfection and dual-luciferase reporter assay. RESULTS Compared with the rats in diabetes control （DC） group, the blood glucose, sympathetic drive indexes and the level of miR-9-5p in PVN were significantly increased, while the SK3 expression in PVN was obviously reduced in the diabetes mellitus （DM） rats. After microinjecion of rAAV-miR-9-5p in PVN, the sympathetic drive indexes, blood glucose, and the number of FosB-positive cells were increased significantly, but the SK3 protein expression was significantly reduced （P <0.05）. However, up-regulation of KCNN3 in PVN had the opposite effect. These responses were obviously enhanced in DM rats compared with DC rats. The results of cell transfection and dual-luciferase reporter assay demonstrated that miR-9-5p bound to the 3’-UTR of KCNN3 and inhibit its expression. CONCLUSION miR-9-5p was up-regulated in PVN of the rats with T2D, and it may mediate sympathoexcitation by targeting KCNN3 . 相似文献