GSDMD-N和p-MLKL蛋白在类风湿关节炎滑膜组织中上调  

Up-regulation of GSDMD-N and p-MLKL in rheumatoid arthritis synovial tissues

作　　者：卢珊[1] 张冰清[2] 叶菜英[1] 朱蕾[1] LU Shan;ZHANG Bing-qing;YE Cai-ying;ZHU Lei(Department of Pharmacology,Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC,Beijing 100005;Department of General Internal Medicine, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, China)

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院基础学院药理学系,北京100005 [2]中国医学科学院北京协和医学院北京协和医院普通内科,北京100730

出　　处：《基础医学与临床》2022年第4期560-564,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81102454);中国医学科学院医学与健康科技创新工程(2021-I2M-1-005);中国医学科学院医学表观中心基金(2017PT31035,2018PT31015,2019PT310017);中央高校基本科研业务费专项资金(3332020013)。

摘　　要：目的探索类风湿关节炎(RA)患者膝关节滑膜组织中细胞焦亡标志性蛋白GSDMD-N和程序性坏死标志性蛋白p-MLKL的表达水平和意义。方法记录入组患者临床资料,包括性别、年龄、红细胞沉降率(ESR)和超敏C反应蛋白(hsCRP)。对RA和骨关节炎(OA)滑膜HE染色,用Krenn评分评估病理滑膜炎程度。提取RA和OA关节滑膜蛋白,利用Western blot检测细胞焦亡和程序性坏死相关蛋白的表达水平,并分析GSDMD-N、p-MLKL与ESR、CRP水平以及病理性滑膜炎的相关性。结果与OA相比,RA关节滑膜中GSDMD-N和p-MLKL的表达水平显著升高(P<0.05),且与ESR和Krenn评分呈正相关(P<0.05),GSDMD-N与CRP水平亦正相关(P<0.05)。结论RA关节滑膜中细胞焦亡和程序性坏死与疾病活动程度和滑膜炎性水平呈正相关,可能参与RA滑膜炎的进程,有望成为RA治疗的潜在靶点。Objective To explore the expression of pyroptosis marker protein GSDMD-N and necroptosis marker protein p-MLKL in rheumatoid arthritis(RA)synovial tissues and potential significance.Methods The clinical data of the enrolled patients were recorded,including gender,age,erythrocyte sedimentation rate(ESR)and hypersensitive C-reactive protein(hsCRP).HE staining and microscopy were performed on RA and osteoarthritis(OA)synovium,Krenn score was used to evaluate the pathological synovitis.The synovial proteins of RA and OA were extracted.The expression of the related proteins of pyroptosis and necroptosis was detected by Western blot,and the correlation of GSDMD-N and p-MLKL with ESR,CRP and pathological synovitis were analyzed.ResultsCompared with OA,the expression level of GSDMD-N and p-MLKL in RA synovial tissues was significantly increased(P<0.05),and was positively correlated with ESR and Krenn score(P<0.05).GSDMD-N was also positively correlated with CRP level(P<0.05).Conclusions Both pyroptosis and necroptosis in RA synovium show at positive correlation with disease activity and synovial inflammation,which might be involved in the process of RA synovitis and be potential targets for the treatment of RA.

关 键 词：类风湿关节炎 GSDMD-N p-MLKL 细胞焦亡 细胞程序性坏死 

分 类 号：R96[医药卫生—药理学]