黑骨藤追风活络胶囊对类风湿关节炎大鼠PI3K/AKT/HIF-1α通路的作用  

Effect of Hei Gu Teng Zhui Feng Huo Luo Capsule on PI3K/AKT/HIF-1α protein signaling pathway in rheumatoid arthritis rats

作　　者：刘杨[1] 姜珊珊 陈向云[1] 杨欣 严福林 曹峰[1] 杨长福[1] 梁江[1] LIU Yang;JIANG Shan-Shan;CHEN Xiang-Yun;YANG Xin;YAN Fu-Lin;CAO Feng;YANG Chang-Fu;LIANG Jiang(Guiyang University of Chinese Medicine,Guiyang 550002,China)

机构地区：[1]贵阳中医学院

出　　处：《中国免疫学杂志》2019年第18期2206-2212,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金(81560817);贵州省一流学科建设项目(QYNYL[2017]005);贵州省科技厅项目(黔科合平台人才[2017]5735号-08);贵州省科技厅项目(黔科合J字[2013]2074号);贵州省教育厅项目(黔教合KY字[2015]438号);贵州省重大基础专项项目(苗药协同创新中心[2015]05号);贵中医博士项目启动基金(贵中医博2012-06号)

摘　　要：目的:观察黑骨藤追风活络胶囊对类风湿关节炎大鼠PI3K/AKT/HIF-1α轴的影响。方法:雄性SD大鼠随机分为空白组、模型组、黑骨藤追风活络胶囊0.315g/kg组、黑骨藤追风活络胶囊0.315g/kg+PI3K抑制剂LY2940020.01g/kg联合给药组。除空白组外,其余各组构建模型。给药5周内测量大鼠足跖厚度,脾脏HE染色观察病理表现,TUNEL法观察脾脏细胞凋亡,免疫蛋白印迹法检测脾脏Caspase-1、3和Cytochrome-C蛋白表达和检测关节滑膜组织p-PI3K、p-AKT、HIF-1α、Bax、Bcl-2蛋白,ELISA试剂盒检测血浆IL-2、IL-4、IL-17表达。结果:与模型组相比,空白组、黑骨藤追风活络胶囊组、联合给药组大鼠足跖肿胀度明显降低;脾脏病理表现明显改变;TUNEL染色显示空白组、黑骨藤追风活络胶囊组、联合给药组脾脏凋亡细胞平均光密度值表达下调;免疫蛋白印迹显示空白组、黑骨藤追风活络胶囊组、联合给药组脾脏内Caspase-1、3和Cytochrome-C表达下降,黑骨藤追风活络胶囊组、联合给药组滑膜组织内Bax表达上调,空白组、黑骨藤追风活络胶囊组、联合给药组p-PI3K、p-AKT、HIF-1α、Bcl-2表达下调;ELISA显示空白组、黑骨藤追风活络胶囊组、联合给药组血浆IL-2、IL-17表达下调,IL-4表达上调。结论:黑骨藤追风活络胶囊可能通过调节PI3K/AKT/HIF-1α轴对类风湿关节炎大鼠炎性反应起到抑制作用。Objective:To investigate the effect of Hei Gu Teng Zhui Feng Huo Luo Capsule(HGT2FHC)on PI3K/AKT/HIF-1αprotein signaling pathway in rheumatoid arthritis rats.Methods:Male SD rats were randomly divided into control group,model group,0.315 g/kg group of HGTZFHL Capsule and 0.315 g/kg group of HGTZFHL Capsule and 0.01 g/kg group of PI3K inhibitor.The model was constructed in all groups except control group.The pedal swelling thickness of rats were measured in five weeks.The pathological features of spleen were observed by HE staining.Apoptosis of spleen cells were observed by TUNEL method.The expression of Caspase-1,3 and Cytochrome-C protein in spleen and p-PI3K,p-AKT,HIF-1α,Bax,Bcl-2 protein in synovial tissue were detected by Western blot.ELISA kit was used to detect the expression of IL-2,IL-4,IL-17 in blood plasma.Results:Compared with the model group,the pedal swelling were significantly decreased in the control group,the HGTZFHL Capsule group and the combined administration group.The pathological manifestation of spleen was changed obviously.The expression of average optical density of apoptotic cells in spleen was down-regulated in the control group,the HGTZFHL Capsule group and the combined administration group by TUNEL staining.Western blot showed that the expression of Caspase-1,3 and Cytochrome-C in spleen decreased in the control group,the HGTZFHL Capsule group and the combined administration group and Bax expression in synovial tissue was up-regulated in the HGTZFHL Capsule group and the combined administration group.The expression of p-PI3K,p-AKT,HIF-1α,Bcl-2 were down-regulated in the control group,the HGTZFHL Capsule group and the combined administration group.ELISA showed that the expression of biood plasma IL-2 and IL-17 were down-regulated and the expression of IL-4 was up-regulated in the control group,the HGTZFHL Capsule group and the combined administration group.Conclusion:HGTZFHL Capsule may inhibit the inflammatory response of rheumatoid arthritis rats by regulating the PI3K/AKT/HIF-1αs

关 键 词：黑骨藤追风活络胶囊 类风湿关节炎 炎症 滑膜病变 

分 类 号：R967[医药卫生—药理学]