清热活血方对CIA大鼠自噬相关蛋白p62表达的影响  

Effect of Qingre Huoxue Recipe on Expression of Autophagy Related Protein p62 in CIA Rats

作　　者：管津智 姜泉[1] 夏聪敏 翟争 张富渊 彭秋伟 李达 巩勋[2] 唐晓颇[2] GUAN Jinzhi;JIANG Quan;XIA Congmin;ZHAI Zheng;ZHANG Fuyuan;PENG Qiuwei;LI Da;GONG Xun;TANG Xiaopo(Beijing University of Chinese Medicine,Beijing 100029,China;Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Shanghai Taikuntang Hospital of Traditional Chinese Medicine,Shanghai 200001,China)

机构地区：[1]北京中医药大学,北京100029 [2]中国中医科学院广安门医院,北京100053 [3]上海泰坤堂中医医院,上海200001

出　　处：《中国中医基础医学杂志》2023年第4期588-592,共5页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金项目(81974568)-基于成破骨细胞平衡探讨清热活血方药调控miRNA-214-ATF4通路抑制类风湿关节炎骨破坏的机制研究;国家自然科学基金项目(82230121)-中西医结合防治类风湿关节炎骨破坏的免疫机制研究;国家重点研发计划项目(2018YFC1705202)-中医药治疗类风湿关节炎的临床队列及疗效评价研究;中国中医科学院科技创新工程项目(CI2021A01501)-活动性类风湿关节炎核心证候的中医药方案优化及优势人群特征研究。

摘　　要：目的 研究清热活血方对胶原诱导关节炎(collagen type Ⅱ-induced arthritis, CIA)大鼠滑膜组织、外周血单个核细胞(peripheral blood mononuclear cells, PBMC)自噬相关蛋白p62的影响,进一步探讨清热活血方防治类风湿关节炎的相关机制。方法 40只SD大鼠随机分成正常组、模型组、清热活血方组、依那西普组,用免疫源性牛Ⅱ型胶原造模,造模成功后各组大鼠分别给予相应药物灌胃,连续治疗28 d后观察大鼠关节肿胀程度,检测大鼠血清肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)及白细胞介素-1β(interleukin-1β, IL-1β)水平、滑膜及PBMC中p62蛋白表达情况。结果 与正常组比较,模型组大鼠出现关节红肿,血清TNF-α、IL-1β水平上升(P<0.01),关节滑膜组织及PBMC中p62 mRNA水平上升(P<0.01),p62蛋白相对含量降低(P<0.01)。与模型组比较,清热活血方组大鼠血清TNF-α、IL-1β含量降低(P<0.01),滑膜组织及PBMC中p62 mRNA水平均降低(P<0.01),p62蛋白相对含量升高(P<0.01)。结论 清热活血方可通过下调CIA大鼠血清TNF-α、IL-1β水平抑制大鼠滑膜组织及PBMC中p62蛋白的转录,减少p62蛋白的消耗,抑制自噬水平而起到抗炎作用。Objective To investigate the effect of Qingre Huoxue Recipe on p62 protein in synovial tissues and peripheral blood mononuclear cells(PBMC)in collagen typeⅡ-induced arthritis(CIA)rats,and to explore the mechanism of Qingre Huoxue Recipe in prevention and treatment in rheumatoid arthritis(RA).Methods Forty SD rats were randomly divided into normal group,model group,Qingre Huoxue Recipe group and etanercept group,and the model was made with typeⅡcollagen.After the model was successfully made,the rats in each group were given corresponding drug,respectively.After continuous treatment for 28 days,the degree of joint swelling of the rats was observed,the levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in serum,the expression of p62 in synovium and PBMC were detected.Results Compared with the normal group,the model group showed increase in joint swelling,serum levels of TNF-αand IL-1β,the expression level of p62 mRNA in synovium and PBMC(P<0.01),but the level of p62 protein was decreased(P<0.01).Compared with model group,serum levels of TNF-αand IL-1β,synovium and PBMCp62 mRNA levels in rats of Qingre Huoxue Recipe group were decreased,while p62 protein levels were increased(P<0.01).Conclusion Qingre Huoxue Recipe can inhibit the transcription of p62 protein in synovial tissue and PBMC of CIA rats by down-regulating the serum levels of TNF-αand IL-1β,thereby reducing the consumption of p62 protein and inhibiting the level of autophagy to play an anti-inflammatory role.

关 键 词：类风湿关节炎 p62蛋白 自噬 滑膜 PBMC 

分 类 号：R285.5[医药卫生—中药学]