摘要
目的探讨独活寄生汤通过NLRP3/caspase-1信号通路调控软骨细胞焦亡影响类风湿关节炎(rheumatoid arthritis,RA)的作用机制。方法动物水平采用佐剂性关节炎(AA)构建RA大鼠模型,将模型大鼠随机分为两组,分别采用中药独活寄生汤和西药依托考昔干预,足趾容积测量仪检测足趾容积评估两组模型大鼠治疗前后关节肿胀情况,并采用ELISA检测治疗前后两组模型大鼠血清中类风湿因子(RF)、白细胞介素-1β(IL-1β)及白细胞介素-18(IL-18)水平。细胞水平通过胞外酸化法诱导大鼠关节软骨细胞,构建RA模型,使用独活寄生汤或依托考昔处理细胞,采用RT-qPCR及Western blotting检测各组细胞中NLRP3、caspase-1、凋亡相关斑点样蛋白(ASC)、IL-1β、IL-18 mRNA及蛋白水平,流式细胞术检测细胞焦亡水平。结果动物实验结果提示,与治疗前相比,独活寄生汤或依托考昔治疗后,RA模型大鼠关节肿胀程度均显著降低,且血清中RF、IL-1β及IL-18水平显著下降。细胞实验结果表明,独活寄生汤与依托考昔干预均可显著下调胞外酸化法诱导的RA模型细胞中NLRP3、caspase-1、ASC、IL-1β、IL-18 mRNA及蛋白水平,并显著抑制RA模型细胞焦亡。结论独活寄生汤通过抑制NLRP3/caspase-1信号通路介导的软骨细胞焦亡缓解类风湿关节炎症状是其发挥药效的途经之一。
Objective The explore the functional mechanism of Duhuo Jisheng Decoction(独活寄生汤)on pyroptosis of chondrocyte in rheumatoid arthritis based on the NLRP3/caspase-1 signaling pathway.Methods In this study,the rat model of RA was established by adjuvant arthritis(AA)at animal level,the model of adjuvant arthritis of rats were randomly divided into two groups,which were treated with Duhuo Jisheng Decoction or Etoricoxib,the toe volume of the rats in two groups before and after treatment was measured by toe volume measuring instrument,and the level of rheumatoid factor(RF),IL-1βand IL-18 in serum of RA rats before and after treatment was mesusred by ELISA kit.At the cellular level,the rheumatoid arthritis model of chondrocyte was induced by extracellular acidification,and Duhuo Jisheng Decoction or Etoricoxib was used to intervene cells,after the treatment,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of NLRP3,caspase-1,ASC,IL-1βand IL-18,and flow cytometry were used to measure the cell pyroptosis rate.Results The results of animal experiment showed that the swelling of joint was decreased,the level of RF,IL-1βand IL-18 was significantly decreased after treatment of Duhuo Jisheng Decoction and Etoricoxib.The results of cell experiment showed that Duhuo Jisheng Decoction or Etoricoxib treatment significantly down regulated the mRNA and protein level of NLRP3,caspase-1,ASC,IL-1βand IL-18 in RA model chondrocyte cells induced by extracellular acidification,and markedly inhibited the pyroptosis of RA model chondrocyte cells.Conclusion One of important ways for Duhuo Jisheng Decoction alleviates rheumatoid arthritis is inhibiting NLRP3/caspase-1 signaling pathway mediated pyroptosis of chondrocyte.
作者
彭程
高明利
于静
赵夜雨
姜泉
张婷婷
PENG Cheng;GAO Mingli;YU Jing;ZHAO Yeyu;JIANG Quan;ZHANG Tingting(Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China;Guang'anmen Hospital of China Academy of Chinese Medical Sciences,Beijing 100053,China)
出处
《辽宁中医药大学学报》
CAS
2021年第9期32-36,共5页
Journal of Liaoning University of Traditional Chinese Medicine
基金
国家重点研发计划“中医药现代化研究”重点专项(2018YFC1705202)
作者简介
彭程(1987-),女,辽宁沈阳人,主管技师,学士,研究方向:医学检验学;通讯作者:高明利(1960-),男,辽宁沈阳人,主任医师,博士研究生导师,硕士,研究方向:中西医结合临床。
