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1.
AIM To explore the effect of semaphorin 4D (Sema4D) on the immune regulation of Th1/Th2 in asthmatic rats induced by respiratory syncytial virus (RSV) and the effect of Kechuanning (KCN) intervention on the asthmatic rats. METHODS Healthy SPF female Wistar rats (n=100) were randomly divided into 10 groups: normal group, model group, Sema4D group, Sema4D antibody group, low, middle and high doses of KCN groups, and Sema4D+low, middle and high doses of KCN groups. Except the rats in normal group, the other rats were treated with RSV combined with ovalbumin (OVA) to induce asthmatic model. The pathological changes of the lung tissue were observed by HE staining, and the levels of interleukin-4 (IL-4), IL-6, IL-8, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in bronchoalveolar lavage fluid (BALF) were measured by ELISA. RESULTS Inflammatory cell infiltration and inflammatory damage in lung tissues of the rats in model group, Sema4D group and Sema4D+low dose of KCN group were observed by HE staining, while these pathological changes were attenuated in Sema4D antibody group, low, middle and high doses of KCN groups, and Sema4D+middle and high doses of KCN groups. Compared with normal group, the levels of IL-4, IL-6, IL-8 and TNF-α in BALF of the rats in the other groups were significantly increased, and the level of IFN-γ was significantly lowered (P<0.05 or P<0.01). Compared with model group, the levels of IL-4, IL-6, IL-8 and TNF-α in Sema4D group were increased, and the content of IFN-γ was decreased (P<0.05 or P<0.01). Compared with model group, the levels of IL-4, IL-6, IL-8 and TNF-α in Sema4D antibody group, low, middle and high doses of KCN groups, and Sema4D+low, middel and high doses of KCN groups were significantly decreased (P<0.01), while the content of IFN-γ was significantly increased (P<0.05 or P<0.01). No significant difference among Sema4D antibody group, Sema4D+middle and high doses of KCN groups, and low, middle and high doses of KCN groups was observed (P>0.05). CONCLUSION Sema4D causes Th1/Th2 immune imbalance and aggravates asthma. Inhibition of Sema4D reduces the production of inflammatory factors and regulates the balance of Th1/Th2. KCN may attenuate RSV-induced immune inflammation of asthmatic rats by inhibiting Sema4D, so as to achieve the anti-asthma effect.  相似文献   

2.
AIM: To explore the possible mechanism of NLR family Pyrin domain-containing protein 3 (NLRP3) inflammasome involved in perfluorooctane sulfonate (PFOS)-induced lung injury in young rats. METHODS: Twenty-eight SD rats (21-day-old) were randomly divided into control (C) group, PFOS (P) group, glyburide (G) group and glyburide + PFOS (GP) group. PFOS exposure model and glyburide protection model were established. The lung specimens were collected for HE staining. The levels of myeloperoxidase (MPO) in the lung tissues, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the bronchoalveolar lavage fluid (BALF) were measured by ELISA. The concentration of PFOS in serum was measured by high-performance liquid chromatography (HPLC). The protein expression of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing CARD (ASC) in the lung tissues was determined by Wes-tern blot. RESULTS: HE staining of lung tissues showed that compared with the control rats, there were obvious inflammatory infiltration in trachea and alveolar interstitium of the rats in P group. Glyburide reduced the inflammatory responses significantly. ELISA results showed that the level of MPO in the lung tissues of the rats in P group was higher than those in other 3 groups (P<0.05). The levels of IL-1β and IL-18 in the BALF of the rats in P group were significantly higher than those in control group and GP group (P<0.05). The results of Western blot showed that the protein levels of NLRP3, caspase-1 and ASC in P group were significantly higher than those in control group and GP group (P<0.01). Immunohistochemical staining results showed that compared with the other 3 groups, the expression of NLRP3 in P group was significantly increased (P<0.01). CONCLUSION: PFOS exposure may lead to lung injury in rats by activating NLRP3 inflammasome and then triggering inflammation, releasing inflammatory factors such as IL-1β. Glyburide specifically inhibits the assembly of NLRP3 inflammasome, suppresses the inflammatory responses and reduces the toxicity of PFOS in lung.  相似文献   

3.
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   

4.
AIM To investigate the effect of forsythiaside A (FA) on immune function in rats with ulcerative colitis and its related mechanism. METHODS Healthy SD rats were randomly divided into 5 groups: control group (no treatment, normal feeding), model group (establishment of rat ulcerative colitis model), and low, medium and high doses of FA groups (treatment of the model rats with FA at 5 mg/kg, 20 mg/kg and 80 mg/kg, respectively). The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in rat colon tissues were measured by colorimetry, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2) and IL-4 were detected by ELISA. The spleen index and thymus index, the percentages of CD3+, CD4+ and CD8+ T-lymphocytes in peripheral blood mononuclear cells （PBMC）, the serum IgA and IgG levels, and the serum complement C3 and C4 levels were also determined. RESULTS The colon tissues of the rats in model group showed obvious inflammation and ulceration, indicating that the animal model was successfully established. Compared with model group, the colonic inflammation and ulceration were significantly attenuated in FA groups, among which the high dose had the best effect. Compared with control group, the spleen index and thymus index of the rars in model group were decreased (P<0.05), MDA content in colon tissues was increased (P<0.05), and SOD activity in colon tissues was decreased (P<0.05). The levels of CD3+, CD4+, CD8+ and CD4+/CD8+ T-lymphocytes in PBMC, and the serum levels of C3, C4 and IL-4 were decreased (P<0.05), while the serum levels of IgA, IgG, TNF-α, and IL-2 were increased in model group as compared with control group. Furthermore, the spleen index and thymus index of the rats in FA groups were increased (P<0.05), the MDA content in the colon tissues was decreased (P<0.05), and the SOD activity in the colon tissues was increased (P<0.05). The levels of CD3+, CD4+, CD8+ and CD4+/CD8+ T-lymphocytes in PBMC, and the serum levels of C3, C4 and IL-4 were increased (P<0.05), while serum IgA, IgG, TNF-α and IL-2 levels were decreased in FA groups as compared with model group (P<0.05). CONCLUSION Forsythiaside A effectively attenuates the colonic lesions in rats with ulcerative colitis, and its mechanism may be related to reinforcement of oxygen free radical scavenging power, alleviation of inflammatory response, and enhancement of immune function.  相似文献   

5.
AIMTo investigate the effect of curcumin (CUR) on autophagy of hepatovyte in rats with lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury (AHI). METHODSThe healthy male Sprague-Dawley (SD) rats were randomized into the control group,AHI group,CUR group, 3-methy-ladenine (3-MA) group and 3-MA+CUR group, with 6 rats in each group. AHI was induced with an intraperitoneal injection of LPS and D-GalN. Liver function was tested 12 h after LPS/D-GalN treatment. Pathological changes of liver tissues were analyzed by HE staining.The amount of autophagic bodies were observed by transmission electron microscopy. The protein levels of autophagy related-proteins LC3 and beclin 1 in livers were detected by Western blot. ELISA were used to examine the serum levels of tumor necrosis factor-α (TNF-α). RESULTSCompared with control group, the serum level of alanine aminotransferase (ALT) and asparated aminotransferase (AST) were significantly increased, hepatic pathological damage were aggravated and serum TNF-α level was significantly increased in AHI group, while the autophagic bodies and the protein levels of LC3 and beclin 1 were increased (P<0.01). Compared with AHI group, the serum level of ALT and AST were significantly decreased, hepatic pathological damage were attenuated and serum TNF-α level was significantly reduced (P?<0.05), while the autophagic bodies and the protein levels of LC3 and beclin 1 were significantly increased in CUR group (P<0.01). Compared with CUR group, the serum level of ALT and AST were significantly increased, hepatic pathological damage were aggravated and serum level of TNF-α was significantly increased in 3-MA group and 3-MA+CUR group, while the autophagic bodies and the protein levels of LC3 and beclin 1 were decreased (P<0.01). CONCLUSION Curcumin protects rats against LPS/D-GalN-induced liver injury, partially due to activation of hepatocyte autophagy in livers.  相似文献   

6.
AIM: To investigate the effects of dexmedetomidine (DEX) on the behaviors and the expression of brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the hippocampus of depressive rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham operation group, model group, and DEX (2.5, 5 and 10 μg/kg) groups. The rats were randomly selected in each group (n=12). The rat depression model was established by chronic unpredictable mild stress and ovariectomy. The rats in DEX groups received daily DEX treatment via intraperitoneal injection for 21 d. The forced swimming immobility time (FSIT) and open-field test were used to evaluate the antidepressant effect of DEX. Escape latency and times of crossing the flat were evaluated by Morris water maze. The histological changes of hippocampal neurons were determined by Nissl staining. The mRNA levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected by RT-qPCR. The protein expression of IL-1β, IL-6, TNF-α and BDNF, and the phosphorylation levels of protein kinase A (PKA), cAMP response element-binding protein (CREB), tropomyosin-related kinase B (TrkB), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mTOR in hippocampus were evaluated by Western blot. RESULTS: Compared with model group, the FSIT was significantly reduced and the spontaneous activity was markedly increased in DEX groups. The damage of the hippocampal neurons was obviously attenuated, the escape latency was obviously decreased, and times of crossing the flat were markedly increased (P<0.05 or P<0.01). The levels of IL-1β, IL-6 and TNF-α were obviously decreased, and the protein levels of p-PKA, p-CREB, BDNF, p-TrkB and p-PI3K, p-Akt, p-mTOR in hippocampal tissues were obviously increased (P<0.05 or P<0.01). CONCLUSION: Dexmedetomidine improves the behaviors and the spatial learning and memory ability of depressive model rats, which may be related to its anti-inflammatory effects, as well as up-regulating the protein levels of BDNF and p-TrkB, and activating PI3K/Akt/mTOR signaling pathway in the hippocampus.  相似文献   

7.
XU Yan  SHU Shi-yu 《园艺学报》2020,36(7):1170-1177
AIM To study the effects of HET0016 on the proliferation and migration of microglia stimulated by lipopolysaccharide (LPS). METHODS Primary microglia from neonatal SD rats were isolated, purified and cultured. CCK-8 assay was performed to detect the effect of HET0016 on the viability of microglia after treatment with LPS. The levels of 20-hydroxyeicosatetraenoic acid （20-HETE）, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by ELISA. The proportion of S phase was evaluated by flow cytometry. The cell migration ability was detected by Transwell assay and scratch wound healing assay. The protein expression of NF-κB p50 and p65 was determined by Western blot. RESULTS LPS induced the increases in the proliferation and migration of microglia and the release of inflammatory cytokines (P<0.05). Compared with LPS group, HET0016 inhibited the cell proliferation and migration (P<0.05), decreased the levels of TNF-α and IL-1β (P<0.05), and reduced the expression of NF-κB p50 and p65 (P<0.05). CONCLUSION HET0016 has inhibitory effects on the proliferation and migration of microglia induced by LPS, and reduces the release of inflammatory cytokines. The mechanism may be related to NF-κB signaling pathway.  相似文献   

8.
AIM: To observe the expression of cluser of differentiation 14 (CD14), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) in periapical tissues of patients with chronic periapical diseases, and to analyze the role of immunopathogenesis of CD14, TNF-α and IL-4 expression in human chronic periapical diseases. METHODS: A total of 88 samples were divided into 3 groups: healthy control group (n=45), chronic periapical abscess group (n=23), and periapical cyst group (n=20). All samples were fixed in 10% buffered formalin and stained with double immunofluorescence for identification of TNF-α-CD14 and IL-4-CD14 double-positive cells in periapical tissues. RESULTS: Compared with healthy control group, the densities of TNF-α-CD14 and IL-4-CD14 double-positive cells in the 2 groups of chronic periapical diseases were increased significantly (P<0.05). Compared with periapical cyst group, the density of TNF-α-CD14 double-positive cells in chronic periapical abscess was increased significantly (P<0.05). The density of IL-4-CD14 double-positive cells in periapical cyst group was significantly higher than that in chronic periapical abscess group (P<0.05). CONCLUSION: There is high expression of TNF-α-CD14 and IL-4-CD14 double-positive cells in the periapical tissues of the patients with chronic periapical abscess and perapical cyst, suggesting that the Th cytokines participate in the immune regulation of periapical diseases, which may be one of the immune mechanisms of the interaction between Th1 and Th2 cytokines.  相似文献   

9.
AIM To explore the possible mechanism of cathepsin C （CTSC） and tumor necrosis factor-α （TNF-α） in coronary heart disease （CHD） by detecting the protein expression of CTSC and TNF-α in human coronary artery tissue. METHODS The coronary artery tissues from 52 cases of CHD and 25 cases of accidental death without any heart disease in the Forensic Judicial Expertise Center of Guizhou Medical University from October 2018 to December 2019 were collected as CHD group and control group, respectively. The coronary artery stenosis and intimal plaque formation were examined by histopathology, the protein expression of CTSC and TNF-α was determined by Western blot, and the intracellular expression of CTSC and TNF-α was analyzed by immunohistochemical staining. RESULTS The results of HE staining showed that the intima of coronary artery in control group was smooth, and no thickening or stenosis was observed. In CHD group, the intima thickened irregularly, atherosclerotic plaques formed, the intima became thinner and the lumen showed eccentric stenosis in varying degrees （P<0.05）. The results of Western blot showed that the expression of CTSC and TNF-α in CHD group was significantly higher than that in control group （P<0.05）. Immunohistochemical staining showed that both CTSC and TNF-α were expressed in the cytoplasm of foam cells, and their positive expression was significantly higher than that in control group （P<0.05）. The results of Pearson moment correlation analysis showed that there was positive correlation between the expression of CTSC and TNF-α in CHD （r2=0.743, P<0.05）. CONCLUSION The up-regulated expression of CTSC in coronary artery tissue may promote the expression of TNF-α and affect the occurrence and development of CHD.  相似文献   

10.
AIM To investigate the protective effect of recombinant human serum albumin (HSA)-thioredox?in (Trx) fusion protein (HSA-Trx) on mice with acute lung injury (ALI) induced by influenza virus infection. METH?ODS: The recombinant HAS-Trx fusion protein was generated by Pichia pastoris expression system. ICR mice were used to establish the animal model of ALI induced by PR8 (H1N1) influenza virus, and the experimental mice were divided into healthy control group, ALI group, ALI+Trx group and ALI+HSA-Trx group, with 10 mice in each group. The bronchoalveolar lavage fluid (BALF) in each group was collected, the total number of cells and the number of alveolar neutrophils were determined, the protein concentration was measured by Coomassie brilliant blue solution method, and the interferon-γ (IFN-γ) content in BALF was detected by ELISA. The lung tissues were collected for hematoxylin and eosin staining. The inducible nitric oxide synthase (iNOS), 8-hydroxydeoxyguanosine (8-OHdG) and 3-nitrotyrosine (NO2-Tyr) in lung tissues were detected by immunofluorescence method. Peroxide concentration in plasma was evaluated using a CR2000RC analyzer. RESULTS HSA-Trx treatment significantly reduced the total number of cells, neutrophils and total protein in BALF of ALI mice (P<0.05), and decreased the levels of 8-OHdG, NO2-Tyr in lung tissue and peroxide in plasma (P<0.05). However, it has no significant inhibitory effect on iNOS and IFN-γ expression (P>0.05). CONCLUSION HSA-Trx inhibits inflammatory response and excessive production of nitric oxide in the lung, thus protecting influ?enza virus-induced ALI mice.  相似文献   

11.
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12.
AIM To investigate the effects of cytochrome P450 （CYP450） epoxygenase/epoxyeicosatrienoic acid （EET） pathway on insulin resistance in obese mice, and to explore the possible mechanisms. METHODS High-fat diet-induced obesity model was established in C57BL/6Cnc mice, and the obese mice were randomly divided into 3 groups, including obesity group （treated with saline; n=10）, EET group （treated with 11,12-EET; n=10） and EET inhibitor 14,15-epoxyeicosa-5（Z）-enoic acid （EEZE） group （n=10）. Normal C57BL/6Cnc mice （n=10） treated with saline served as control. Protein expression of CYP2J2 （one of CYP450 epoxygenases） and hypoxia-inducible factor-1α （HIF-1α） was measured by Western blot. Vessel-like structure was detected by immunofluorescence staining. The serum levels of insulin, tumor necrosis factor-α （TNF-α）, interleukin （IL）-1β, IL-6 and monocyte chemoattractant protein-1 （MCP-1） were measured by ELISA. RESULTS In obese mice, homeostasis model assessment of insulin resistance （HOMA-IR） values were increased, the protein level of CYP2J2 was reduced, and the protein level of HIF-1α was increased in adipose tissues as compared with the controls （P<0.05）. The serum levels of MCP-1, IL-1β, IL-6 and TNF-α were also significantly increased in obese mice （P<0.05）. After treatment with 11, 12-EET, the HOMA-IR values were decreased compared with vehicle-treated obese mice, HIF-1α expression levels were decreased in the adipose tissue, and the serum levels of MCP-1, IL-1β, IL-6 and TNF-α were reduced （P<0.05）. Immunohistochemical results of adipose tissue from vehicle-treated obese mice showed a marked decrease in vessel-like structures （CD31-positive） compared with normal control mice （P<0.05）. EET treatment significantly increased the newly formed vessel-like structures in the visceral adipose tissues of obese mice as compared with vehicle-treated obese mice （P<0.05）. CONCLUSION High-fat diet-induced obesity and insulin resistance are closely related to the CYP450 pathway. Exogenous EETs effectively decrease obesity-induced insulin resistance possibly through pro-angiogenesis and attenuation of hypoxia and inflammation.  相似文献   

13.
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   

14.
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   

15.
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   

16.
AIM To investigate the effect of microRNA-92b-5p （miR-92b-5p） on renal injury and inflammatory response in diabetic nephropathy （DN） rats and its mechanism. METHODS The rats were divided into control group， DN group， lentiviral negative control （LV-NC） group， LV-miR-92b group， LV-high mobility group protein B1 （LV-HMGB1） group and miR-92b+HMGB1 group， with 15 rats in each group. After fasting for 12 h， the model rats were intraperitoneally injected with streptozotocin at dose of 60 mg/kg， and the control rats were intraperitoneally injected with an equal volume of citrate buffer. Three days later， the rats in each treatment group were intravenously injected with 100 μL LV-NC， LV-miR-92b and LV-HMGB1 （1×1011 U/L） twice a week for 8 consecutive weeks. Urinary protein， blood glucose， blood urea nitrogen and serum creatinine were detected by an automatic biochemical analyzer. The expression of miR-92b-5p and HMGB1 mRNA was detected by RT-qPCR. The targeting relationship between miR-92b-5p and HMGB1 was verified by dual-luciferase reporter assay. HMGB1 expression in kidney tissue was detected by Western blot. The kidney damage was observed by HE staining. The apoptosis was detected by flow cytometry. The levels of interleukin-6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） in renal tissues were detected by ELISA. RESULTS In DN model rats， miR-92b-5p was down-regulated， while HMGB1 was highly expressed. There was a binding site between miR-92b-5p and HMGB1 3'-untranslated region. High expression of miR-92b-5p inhibited the luciferase activity of the wild-type HMGB1 plasmid （P<0.01）， but had no effect on the luciferase activity of the mutant HMGB1 plasmid. Compared with DN group， urinary protein， blood glucose， serum creatinine and blood urea nitrogen in LV-miR-92b group were significantly reduced （P<0.01）. The degree of hyperplasia， swelling and inflammatory cell infiltration of glomerular mesangium and basement membrane tubules， the apoptosis rate of renal tissues， and the content of IL-6， IL-1β and TNF-α in renal tissues were significantly decreased （P<0.01）. Co-transfection of LV-HMGB1 significantly reversed the effect of miR-92b-5p on DN rats. CONCLUSION miR-92b-5p reduces renal injury and inflammatory response in DN rats by targeting HMGB1 and down-regulating its expression.  相似文献   

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18.
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   

19.
苹果miR396家族鉴定及在不定根发育过程中的表达分析   总被引：1，自引：0，他引：1  
分析了苹果miR396家族进化特性及其在苹果不定根发育过程中的表达模式。结果表明：苹果miR396家族有4条成熟体和7条前体序列（pre-miRNA）。Mfold预测显示Pre-miR396家族7个成员序列均可形成典型稳定的茎环二级结构,最小折叠自由能介于–62.9 kal ? mol-1（pre-miR396b）~–51.9 kal ? mol-1（pre-miR396g）之间。系统发育进化树分析显示,pre-miR396家族亲缘关系可分为3个亚组（G1、G2、G3）,每个亚组内基因数量不同,分别含有11、9、19个。靶基因预测显示,苹果miR396靶基因包括MdGRF1、MdGRF2和MdGRF5等,降解组测序进一步验证了miR396对其候选靶基因MdGRF1、MdGRF2和MdGRF5的剪切关系。苹果miR396家族成员在侧根和果实中的表达量显著高于其他组织,其候选靶基因表达量则在花芽和腋芽中显著高于其他组织;不定根发育过程中,miR396家族不同成员表达模式存在显著差异,整体上呈上调表达趋势,其候选靶基因呈下调表达趋势;外源IBA处理显著诱导miR396家族成员的表达,尤其是在不定根诱导期和根系生长期更为显著。  相似文献   

20.
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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