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 expression of spleen tyrosine kinase (SYK) in 2 murine cholangiocarcinoma (CCA) progressive models and human CCA tissues, and to explore the effects of SYK expression on the polarization of M2 macrophages. METHODS SD rats were given drinking water containing thioacetamide (TAA) daily. BALB/c mice were treated with left median bile duct ligation combined with diethylnitrosamine (DEN) administration. The expression of SYK and M2 macrophage infiltration (CD163) in the animals and human CCA tissues were detected by immunohistochem?istry, and their correlation was analyzed. Ten SD rats, which were given drinking water containing TAA daily for 24 weeks, were randomly divided into control group (n =5) and SYK inhibitor group (n =5). After the rats received SYK inhibitor through gavage for 4 weeks, the effects of SYK inhibitor on tumor growth and macrophage polarization were analyzed. RESULTS The hepatic bile duct hyperplasia, dysplasia (or cholangioma), and CCA occurred at different time points in the rats and mice. During the development of CCA, SYK expression was gradually increased (P <0.01), accompanied by enhanced infiltration of M2 macrophages, while the M1 macrophages were decreased in the hepatic bile duct tissues (P <0.01). SYK and CD163 expression levels were significantly up-regulated (P <0.01), and a positive correlation (r =0.57, P <0.01) in human CCA tissues was observed. In the rat CCA model, the number of tumor nodules and infiltration of M2 macrophages in SYK inhibitor group were decreased compared with its control group (P <0.01). CONCLUSION In the murine CCA models, SYK expression was progressively increased during the evolution of CCA, which may promote tumor progression via the polarization of M2 macrophages, and SYK inhibitor effectively inhibits the tumor growth and M2 macrophage polarization in the rat CCA model. 相似文献
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AIM To investigate the effect of NOD-like receptor family caspase recruitment domain containing 3 (NLRC3 ) expression knock-down on the viability and apoptosis of normal human bronchial epithelial BEAS-2B cells and its mechanism. METHODS The small interfering RNA (siRNA) fragments of NLRC3 gene were transfected into BEAS-2B cells using Lipofectamine 2000 transfection reagent to knock down the NLRC3 expression. The interference fragment was screened by RT-qPCR. The cell viability was measured by MTT assay. The mitochondrial membrane potential was detected by JC-1 staining. The apoptotic rate was analyzed by flow cytometry with annexin V-FITC/PI staining. The protein expression levels of Bcl-2 and Bax were determined by Western blot. RESULTS The interference segment 3 of NLRC3 gene (siNLRC3-3) displayed the best interference effect on NLRC3 expression in BEAS-2B cells (P <0.01). Knock-down of NLRC3 expression in BEAS-2B cells enhanced the cell viability (P <0.01). Knock-down of NLRC3 increased the mitochondrial membrane potential, and decreased the apoptotic rate (P <0.05). Moreover, knock-down of NLRC3 significantly up-regulated Bcl-2 protein expression and significantly down-regulated Bax protein expression (P <0.01). CONCLUSION Knock-down of NLRC3 expression enhances the viability and inhibits the apoptosis of BEAS-2B cells, which may be related to increase in the expression of Bcl-2 protein and decrease in the expression of Bax protein. 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 effect of hyperbaric oxygen (HBO) on synaptic damage of hippocampal neurons in APP/PS1 transgenic (TG) mice and its possible mechanism. METHODS The 6-month-old male APP/PS1 TG mice were randomly divided into TG group, HBO group and cAMP response element binding protein (CREB) inhibitor H89 group, with 10 mice in each group. Ten male wild-type (WT) C57BL/6 mice of the same age were used as negative control group (WT group). The mice in HBO and H89 groups were treated with HBO for 6 cycles, while the mice in WT group and TG group were not treated. The learning and memory abilities were observed by Morris water maze. The nesting ability of the mice was detected by nesting test. The Nissl bodies in hippocampal neurons were observed by Nissl staining. The mRNA expression of CREB and brain-derived neurotrophic factor (BDNF) in hippocampus was detected by real-time PCR. The protein levels of synapsin (SYN), postsynaptic density protein 95 (PSD95), growth-associated protein 43 (GAP43), CREB, phosphorylated CREB (p-CREB) and BDNF in the hippocampus were determined by Western blot. RESULTS Compared with WT group, the learning and memory abilities of the mice in TG group were signilficantly reduced (P <0.05). In addition, the nesting score, the number of Nissl bodies in the hippocampal neurons, the mRNA expression of CREB and BDNF, and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also decreased significantly (P <0.05). Compared with TG group, the learning and memory abilities of the mice in HBO group were improved (P <0.05). Meanwhile, the nesting scores of the mice were significantly increased (P <0.05), the neurons in the hippocampus were arranged neatly, and the number of Nissl bodies, the relative mRNA expression of CREB and BDNF,and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also increased significantly (P <0.05). Compared with HBO group, the mice in H89 group had poor learning and memory abilities, lowered nesting scores and decreased number of Nissl bodies. Futhermore, the relative mRNA expression of CREB and BDNF, and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also decreased significantly (P <0.05). CONCLUSION HBO improves the learning and memory abilities of APP/PS1 TG mice, and its mechanism may be related to activating the CREB/BDNF signaling pathway to reduce synaptic damage of hippocampal neurons in mice. 相似文献
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AIM To investigate the role of fatty acid translocase (FAT/CD36) on differentiation of monocytes to macrophages. METHODS Human monocyte THP-1 cells were treated with phorbol 12-myristate 13-acetate (PMA) at 0, 100 and 200 μg /L. Small interfering RNA (siRNA) targeting CD36 (siCD36) was employed to knock down the expression of CD36 in THP-1 cells. The CD36 over-expression (CD36OE) cell line was constructed by transfection with a recombinant lentivirus containing CD36 cDNA. Optical microscopy and crystal violet staining were used to detect the monocyte morphological changes and adhesion ability. The protein expression of CD36 was measured by flow cytometry and Western blot. The mRNA levels of CD36, CD11b and CD80 were detected by real-time PCR. The protein levels of extracellular signal-regulated kinase (ERK） and Src tyrosine kinase were determined by Western blot. RESULTS The cellular adhesiveness of THP-1 cells was elevated in the process of monocytes differentiation, and the expression of CD36 was increased in this process as well (P <0.01). siCD36 was transfected into the THP-1 cells (CD36i group) and the silencing efficiency was approximately 80%. The cell surface area and cellular adhesiveness were significantly decreased in CD36i group compared with scrambled siRNA (NCi) group (P <0.01). The mRNA levels of CD11b and CD80 were decreased in CD36i group compared with NCi group (P <0.01). The cell surface area and cellular adhesiveness were increased in CD36OE group compared with empty vector (vector) group (P <0.05). The mRNA levels of CD11b and CD80 were increased in CD36OE group compared with vector group (P <0.01). The phosphorylation levels of ERK and Src were decreased in CD36i group compared with NCi group (P <0.05). CONCLUSION CD36 promotes the differentiation of human monocyte THP-1 cells to macrophages by increasing the phosphorylation of Src and further activating ERK. 相似文献
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AIM To investigate the expression of histone chaperone anti-silencing function 1B （ASF1B） in prostate cancer cells and its effect on cell viability in vitro . METHODS Human prostate cancer PC-3 cells were used, and knockdown of ASF1B was conducted by small interfering RNA （siRNA） transfection into the cells. The cells were divided into control group, siRNA negative control vector （mock） group and siRNA-ASF1B group. The viability of the PC-3 cells treated with ASF1B-siRNA for 12, 24 and 48 h was measured by MTT assay. Flow cytometry was used to analyze cell apoptosis and cell cycle distribution. The mRNA expression of apoptosis-related molecules was detected by RT-qPCR, and the expression levels of MAPK/JNK/ERK signaling pathway-related proteins were determined by Western blot. RESULTS The protein level of ASF1B in the normal cells （benign prostatic hyperplasia） was significantly lower than that in the PC-3 cells （P <0.01）. Compared with control group and mock group, the protein expression level of ASF1B in the PC-3 cells transfected with siRNA-ASF1B plasmid and the viability of the PC-3 cells were significantly decreased （P <0.01）. The apoptotic rate of the PC-3 cells transfected with siRNA-ASF1B plasmid was significantly higher than that in control group （P <0.01）, and the cell cycle was arrested at G1 phase. The mRNA levels of p53, caspase-3, Bax and PARP-1 in the PC-3 cells transfected with siRNA-ASF1B plasmid were up-regulated compared with those in control group and Mack group （P <0.01）. In addition, the protein levels of MAP2K4 and p-JNK in the PC-3 cells in siRNA-ASF1B group were significantly higher than those in mock group （P <0.01）, while the protein level of p-ERK was significantly lower than that in mock group （P <0.01）. CONCLUSION ASF1B silencing induces G1 arrest and promotes apoptosis of PC-3 cells. Activating MAPK/JNK/ERK signaling pathway may be a possible contributor to the anti-prostate cancer effect of siRNA-ASF1B. 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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AIM To investigate the effect of interleukin-33 (IL-33 )-modified bone marrow mesenchymal stem cells (BMSCs) on sepsis-induced acute kidney injury (AKI) in rats and the expression of myeloid differentiation factor 88(MyD88). METHODS A septic rat model was established by cecal ligation and puncture. The SD rats (n =80) were randomly divided into control group, model group, negative transfection group (transplanting untransfected BMSCs) and IL-33 transfection group (transplanting BMSCs transfected with IL-33 ), with 20 in each group. Survival rates of the rats within 72 h in the 4 groups were compared. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured before, and 24, 48 and 72 h after transplantation. The kidney pathological damage was observed by HE staining, and the apoptosis of renal cells was detected by TUNEL method 72 h after transplantation. Western blot was used to detect the protein expression levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4) and MyD88. RESULTS The survival rate of the rats in model group was significantly lower than that in control group (P <0.05). The survival rate of the rats in IL-33 transfection group was higher than that in model group and negative transfection group (P <0.05). The levels of SCr and BUN in model group were higher than those in control group (P <0.05). The levels of SCr and BUN in IL-33 transfection group were significantly reduced after transplantation, and were lower than those in model group and negative transfection group (P <0.05). The renal tissue pathological injury score in model group was significantly higher than that in control group (P <0.05). Compared with model group and negative transfection group, the renal tissue pathological injury score in IL-33 transfection group was significantly reduced (P <0.05). The proportion of apoptotic cells in the kidney tissues in model group were higher than that in control group (P <0.05). Compared with model group and negative transfection group, the proportion of apoptotic cells in the kidney tissues in IL-33 transfection group was significantly reduced (P <0.05). The protein expression levels of IL-1β, IL-6, TNF-α, TLR4 and MyD88 in model group were significantly higher than those in control group (P <0.05). Compared with model group and negative transfection group, the protein expression levels of IL-1β, IL-6, TNF-α, TLR4 and MyD88 in IL-33 transfection group were significantly decreased (P <0.05). CONCLUSION IL-33 gene-modified BMSCs significantly improve the renal function of AKI rats with sepsis. The mechanism may be related to IL-33 regulating TLR4/MyD88 signaling pathway and inhibiting renal inflammatory response. 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 explore the effect of inositol 1, 4, 5-trisposphate receptor (IP3R) in luteinizing hormone-epidermal growth factor receptor (LH-EGFR)-induced oocyte meiotic resumption. METHODS: Models of mouse cumulus-oocyte complexs (COCs) culture and follicle culture in vitro were generated to study the effects of 2-aminoethyl diphenyl borate (2-APB) and heparin (IP3R specific inhibitors) on LH/EGF-induced oocyte meiotic resumption and EGF-induced cumulus cell expansion. Real-time PCR was used to detect the mRNA expression of cumulus expansion-related factors. The changes of the intracellular calcium level were monitored using Fluo 3-AM, and the cGMP level was measured by ELISA. RESULTS: The inhibitors of IP3R, 2-APB and heparin, dramatically reversed EGF-induced oocyte maturation (P <0.05) and decreased cGMP levels in COCs (P <0.05). In addition, 2-APB and heparin reversed EGF-induced cumulus expansion, and significantly inhibited EGF-induced cumulus expansion-related factor expression (P <0.05). The activation of IP3R increased intracellular calcium level, and the study found that 2-APB and heparin dramatically reversed EGF-induced elevation of calcium level in cumulus cells (P <0.05). Follicular culture in vitro showed that 2-APB and heparin significantly reversed the LH-induced oocyte maturation (P <0.05). CONCLUSION: LH-EGFR signaling pathway increases calcium level in cumulus cells through IP3R, resulting in meiotic resumption. 相似文献
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MA Dong-xue GAO Wei-juan LIU Zhen-yi ZHANG Hong-jun WANG Jia-ying DONG Xian-hui 《园艺学报》2021,36(12):2198-2204
AIM To explore the effect of compound of Epimedium , Astragalus and Radix Puerariae on the expression of a disintegrin and metalloproteinase 10 （ADAM10） in Aβ-induced hippocampal neuron HT22 cells with or without hepcidin （HAMP） expression knock-down for analyzing the pathogenesis of Alzheimer disease （AD） at cell level. METHODS Hippocampal neuron HT22 cells were cultured in vitro and randomly divided into 7 groups： control group, Aβ group （Aβ25-35-induced HT22 cells）, RNAi group （HAMP gene was silenced in HT22 cells）, Aβ+RNAi group （HAMP gene expression in Aβ25-35-induced HT22 cells was silenced）, Aβ+TCM group （Aβ25-35-induced HT22 cells were treated with Epimedium , Astragalus root and Radix Puerariae effective components）, RNAi+TCM group （HT22 cells with HAMP gene silence were treated with Epimedium , Astragalus root and Radix Puerariae effective components） and Aβ+RNAi+TCM group （Aβ25-35-induced HT22 cells with HAMP gene silence were treated with Epimedium , Astragalus root and Radix Puerariae effective components）. The silence efficiency of HAMP siRNA was detected by qPCR and Western blot. The ADAM10 expression in each group was determined by immunofluorescence, qPCR and Western blot. RESULTS The HAMP siRNA-3 sequence had the highest interference efficiency. Compared with control group, the expression levels of ADAM10 in Aβ group, RNAi group and Aβ+RNAi group were decreased （P <0.05）. Compared with Aβ group,the expression levels of ADAM10 in Aβ+RNAi group was also decreased （P <0.05）, and the expression levels of ADAM10 in Aβ+TCM group was increased （P <0.05）. Compared with RNAi group, the expression levels of ADAM10 in Aβ+RNAi group was decreased （P <0.05）, while the expression levels of ADAM10 in RNAi+TCM group was increased （P <0.05）. Compared with Aβ+RNAi group, the expression levels of ADAM10 in Aβ+RNAi+TCM group was increased （P <0.05）. CONCLUSION The effective components of Epimedium , Astragalus and Radix Puerariae compound promotes the expression of ADAM10 in Aβ25-35-induced HT22 cells, which mechanism may be related to the expression of HAMP. 相似文献
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AIM To investigate the effect of sinomenine (SN) on the damage of human neuroblastoma SK-N-SH cells induced by 1-methyl-4-4 phenylpyridine (MPP+) and its mechanism for exploring the pathogenesis of Parkinson disease. METHODS SN was used to treat MPP+-induced SK-N-SH cells. The levels of malondialdehyde (MDA) and glutathione (GSH) in cell culture supernatants were measured by ELISA. The apoptosis was analyzed by flow cytometry. The protein expression levels of Bcl-2 and Bax were determined by Western blot. The expression levels of long noncoding RNA ANRIL and microRNA-626 (miR-626) were detected by RT-qPCR. Dual-luciferase reporter assay was used to evaluate the relationship between ANRIL and miR-626. After ANRIL small interfering RNA was transfected into SK-N-SH cells, the effects of ANRIL expression knock-down on MPP+-induced SK-N-SH cell apoptosis, the protein expression levels of Bcl-2 and Bax, and the levels of MDA and GSH in cell culture supernatants were examined. RESULTS After treatment with MPP+, the apoptotic rate, Bax protein level and ANRIL expression in SK-N-SH cells were increased (P <0.05), and the Bcl-2 protein level and miR-626 expression were decreased (P <0.05). The level of MDA in cell culture supernatants was increased (P <0.05), and the level of GSH was decreased (P <0.05). After SN treatment or ANRIL expression knock-down, decreased apoptotic rate, Bax protein level and ANRIL expression (P <0.05), and increased Bcl-2 protein level and miR-626 expression in MPP+-induced SK-N-SH cells were observed (P <0.05). The level of MDA in the cell culture supernatants was decreased (P <0.05), and the level of GSH was increased (P <0.05). CONCLUSION SN attenuates MPP+-induced damage in SK-N-SH cells by regulating ANRIL/miR-626 signaling pathway. 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 observe the effect of tanshinone ⅡA on liver lipid deposition and ferroptosis-related protein expression in ApoE -/- mice. METHODS Thirty-two ApoE -/- mice were randomly divided into model group, high-dose (60 mg/kg) tanshinone ⅡA group, low-dose (30 mg/kg) tanshinone ⅡA group and simvastatin group, and C57BL/6J mice (n =8) were used as normal control group. The mice in normal control group were given the basic feeding, while the others were given high-fat diet. The mice in tanshinone ⅡA groups and simvastatin group were given corresponding drugs. The mice in normal control group and model group were intraperitoneally injected with equal volume of saline. Eight weeks later, the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were tested by automatic biochemistry analyzer. The liver tissues were stained with HE and oil red O. The contents of reactive oxygen species (ROS) and glutathione (GSH) in liver tissues of the mice were measured by commercially available kits. The liver glutathione peroxidase 4 (GPX4) and p53 were detected by immunohistochemical method. The protein and mRNA expression levels of ferroptosis-related factors GPX4, xCT/SLC7A11, p53 and ferritin heavy chain 1 (FTH1) were determined by Wes automatic Western blot quantitative analysis system and RT-qPCR. RESULTS Compared with normal control group, the serum levels of TC, TG and LDL-C in model group were increased significantly (P <0.05 or P <0.01), and HDL-C did not change significantly. The fat vacuoles were clearly visible in liver tissue. The content of ROS in liver tissue was increased significantly,and GSH was decreased significantly (P <0.01). The mRNA and protein expression levels of p53 were increased significantly, and GPX4, xCT/SLC7A11 and FTH1 were decreased significantly (P <0.05 or P <0.01). Compared with model group, tanshinone ⅡA significantly decreased the serum levels of TC, TG and LDL-C (P <0.05 or P <0.01), and HDL-C did not change significantly. High-dose and low-dose tanshinoneⅡA also significantly decreased the degree of steatosis, and the size of lipid droplets. The content of ROS in liver tissues was decreased significantly, and GSH was increased significantly (P <0.01). The mRNA and protein expression levels of GPX4, xCT/SLC7A11 and FTH1 were increased significantly, and p53 were decreased significantly (P <0.05 or P <0.01). CONCLUSION Tanshinone ⅡA reduces liver lipid deposition and lipid peroxidation damage in ApoE -/- mice, which may be related to the intervention of ferroptosis-related proteins in the liver cells. 相似文献
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JIN Bu JI Fang-fang ZUO An-jun LIU Hui-ting QI Lin HE Yun WANG Qing-yao ZHAO Peng 《园艺学报》2020,36(6):1034-1041
AIM To investigate the role of trimethylamine N -oxide （TMAO） in T-tubule in cultured adult mouse cardiomyocytes. METHODS T-tubule imaging was used to detect T-tubule network in cardiomyocytes. Ca2+ handling dysfunction was identified by confocal Ca2+ imaging. Tubulin densification and polymerization in the cardiomyocytes were assessed by Western blot and immunofluorescence staining. Echocardiography was used to detect cardiac function in the mice fed on TMAO and chow diet. RESULTS Compared with control group, the T-tubule density and T-tubule power of the mouse cardiomyocytes cultured with TMAO were significantly decreased (P <0.01). Compared with control group, the mean amplitude of Ca2+ transients in TMAO group was decreased (P <0.01), while the time to reach the Ca2+ transient peak and the dyssynchrony index increased (P <0.01). Compared with control group, the power of junctophilin-2 (JPH2） in the mouse cardiomyocytes treated with TMAO was decreased (P <0.01). Significant JPH2 accumulation was observed at the edge of the cardiomyocytes (P <0.01). Compared with control group, the microtubule density in TMAO group was significantly higher (P <0.01), and microtubule aggregation was enhanced (P <0.01). Compared with the mice in control group fed on a normal diet, the TMAO-fed mice had significantly lower systolic function and left ventricular ejection fraction (P <0.05). CONCLUSION TMAO impairs cardiac function via the promotion of tubulin polymerization, subsequent JPH2 translocation and T-tubule remodeling, which provides a novel mechanism for the relationship between heart failure and elevated TMAO. 相似文献