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作 者:邓龙飞[1] 汪永忠[2] 韩燕全[2] 姜辉[2]
机构地区:[1]安徽中医药大学研究生部,安徽合肥230038 [2]安徽中医药大学第一附属医院,国家中医药管理局中药制剂三级实验室,安徽合肥230031
出 处:《细胞与分子免疫学杂志》2015年第2期153-158,共6页Chinese Journal of Cellular and Molecular Immunology
基 金:安徽省人事厅人才基金(2005Z035);国家中医药重点学科临床中药学建设项目(国中医药人教发[2012]32号)
摘 要:目的研究威灵仙总皂苷(TSC)对佐剂性关节炎(AA)大鼠的JAK2/STAT3信号通路的作用机制。方法雄性SD大鼠60只,随机分为6组,每组10只。除正常组外,采用Freund完全佐剂诱导AA大鼠模型。造模第12天,灌胃给予相应药物,1次/d,连续16 d,观察药物对AA大鼠体质量及足肿胀度的影响;取固定部位踝关节组织,HE染色观察病理学改变;实时荧光定量PCR法测定滑膜细胞中Janus激酶2(JAK2)、信号转导子和转录激活子3(STAT3)mRNA表达;Western blot法检测磷酸化JAK2及非磷酸化JAK2(p-JAK2、JAK2)、磷酸化STAT3及非磷酸化STAT3(p-STAT3、STAT3)的蛋白表达。结果 TSC可有效缓解AA大鼠体质量减轻及明显抑制AA大鼠足肿胀,明显改变炎细胞浸润,减少血管翳生成,减轻组织增生,有效抑制JAK2、STAT3 mRNA表达及降低p-JAK2/JAK2、p-STAT3/STAT3的相对表达。结论 TSC降低AA大鼠JAK2、STAT3 mRNA表达并抑制p-JAK2/JAK2、p-STAT3/STAT3相对表达,抑制JAK2/STAT3信号通路。Objective To evaluate the effect of total saponins of Clematis (TSC) on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAI-3) signal transduction pathway in adjuvant-induced arthritis (AIA) rats and investigate the probable mechanisms. Methods Sixty male SD rats were randomized divided into six groups: normal group, model control group, (50, 100,200 mg/kg) TSC group, and tripterygium glycosides tablet (10 mg/kg) group (10 rats in each group). Except the normal group, AA models were induced with Freund's complete adjuvant. Twelve days after modeling, corresponding drugs were given to rats by intragastric administration, q. d, for 16 days. Then, the effects of drugs on the body mass and paw swelling of AA rats were observed, and ankle-joint samples were taken to examine the degree of AA by HE staining. Moreover, real-time fluorescent quantitative PCR was performed to detect the expressions of JAK2 and STAT3 mRNA, and Western blotting to determine the expression of p-JAK2, JAK2, p-STAT3, and STAT3 protein. Results Compared with the model group, TSC not only effectively alleviated the body mass loss and significantly inhibited paw swelling in AA rats, but also significantly inhibited inflammatory cell infiltration, pannus formation and tissue proliferation. Furthermore, TSC treatment obviously decreased mRNA expressions of JAK2 and STAT3 as well as the relative expressions of p-JAKZ/JAK2 protein and p-STAr3/STAI3 protein in synovial tissues. Conclusion TSC can inhibit JAK2/STAT3 signal pathway by decreasing the expressions of JAK2 and STAT3 mRNA and the relative expressions of p-JAK2/JAK2 protein and p-STAT3/STAT3 protein of synovial tissues in AA rats.
关 键 词:佐剂性关节炎 威灵仙总皂苷 大鼠 JAK2/STAT3信号通路
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