来源：风湿病与关节炎,2022,11（10）:1-6.

佐剂性关节炎大鼠外周血单个核细胞中hsa-miRNAs的表达及新风胶囊干预研究

（基础研究）

文建庭¹，刘　健²，姜　辉²，孙艳秋¹，王　馨¹，王　杰¹，周　琴¹，丁　香¹，陈晓露¹，张先恒¹

　　【摘　要】目的：探究佐剂性关节炎（AA）大鼠外周血单个核细胞（PBMCs）中人微小RNAs（hsa-miRNAs）的表达及新风胶囊（XFC）干预研究。方法：建立AA大鼠模型，造模后第12天开始给药，将大鼠随机分为正常组（NC组）、模型组（MC组）、XFC低剂量组（L-XFC组）、XFC中剂量组（M-XFC组）、XFC高剂量组（H-XFC组）。给药30 d后，观察各组大鼠体质量、足跖肿胀度、关节炎指数（AI）的变化；RT-qPCR法检测PBMCs中miRNAs的表达；ELISA法检测血清中C反应蛋白（CRP）、抗环瓜氨酸肽抗体（抗CCP抗体）、类风湿因子（RF）、白细胞介素（IL）-11、IL-17、IL-4、IL-10的表达。结果：①致炎前，各组大鼠体质量、足跖肿胀度及AI比较，差异无统计学意义（P > 0.05）；致炎12 d，各组大鼠足跖肿胀度和AI均显著升高（P < 0.01）；XFC给药后，各组大鼠体质量、足跖肿胀度、AI得到显著改善。②与NC组相比，MC组hsa-miR-146a-3p、hsa-miR-31-5p、hsa-miR-29c-3p、hsa-miR-597-3p mRNA表达显著降低（P < 0.01），CRP、RF、抗CCP抗体、IL-17、hsa-miR-3184-5p mRNA表达显著升高（P < 0.01）；XFC治疗后，上述指标得到显著改善。③Spearman相关性分析结果显示，hsa-miR-146a-3p与足跖肿胀度、CRP、RF、IL-11呈显著负相关，与IL-4呈显著正相关（P < 0.05）；hsa-miR-31-5p与AI、RF、IL-17呈负相关，与IL-10呈正相关（P < 0.05）；hsa-miR-29c-3p与RF、IL-11呈负相关（P < 0.05）；hsa-miR-3184-5p与IL-4呈负相关（P < 0.05）。结论：AA大鼠PBMCs中存在差异表达的hsa-miRNAs，与免疫炎症指标具有显著相关性，XFC在改善免疫炎症指标的同时，也能改善miRNAs，其机制有待进一步研究。

　　【关键词】　类风湿关节炎；佐剂性关节炎；微小RNAs；新风胶囊；干预研究；大鼠

Expression of hsa-miRNAs in Peripheral Blood Mononuclear Cells of Adjuvant Arthritis Rats and Intervention of Xinfeng Capsule（新风胶囊）

WEN Jian-ting,LIU Jian,JIANG Hui,SUN Yan-qiu,WANG Xin,WANG Jie,ZHOU Qin,DING Xiang,CHEN Xiao-lu,ZHANG Xian-heng

　　【ABSTRACT】Objective:To investigate the expression of hsa-miRNAs in peripheral blood mononuclear cells（PBMCs）of adjuvant arthritis（AA）rats and the intervention of Xinfeng Capsule（新风胶囊,XFC）.Methods:The AA rat model was established,and the drug was administered on the 12 th day after the model was established.The rats were randomly divided into a normal group（NC group）,a model group（MC group）,a low-dose XFC group（L-XFC group）,a medium-dose XFC group（M-XFC group）,and a high-dose XFC group（H-XFC group）.After 30 days of administration,the changes of body mass,footpad swelling,and arthritis index（AI）of the rats in each group were observed.The expression of miRNAs in PBMCs was detected by RT-qPCR.The expressions of CRP,anti CCP antibody,RF,interleukin IL-11,IL-17,IL-4 and IL-10 in serum were detected by ELISA.Results:①There was no significant difference（P > 0.05）in body mass,footpad swelling and AI of rats in each group before inflammation;twelve days after inflammation,the degree of footpad swelling and AI of rats in each group increased significantly（P < 0.01）;After administration of XFC,body mass,footpad swelling and AI were significantly improved.②Compared with the NC group,the expressions of hsa-miR-146a-3p,hsa-miR-31-5p,hsa-miR-29c-3p,and hsa-miR-597-3p mRNA in the MC group decreased significantly（P < 0.01）,while the expressions of CRP,RF,anti CCP antibody,IL-17,hsa-miR-3184-5p mRNA in the MC group increased significantly（P < 0.01）;After treatment with XFC,the above indicators were significantly improved.③Spearman correlation analysis showed that hsa-miR-146a-3p was significantly negatively correlated with footpad swelling,CRP,RF and IL-11,and significantly positively correlated with IL-4（P < 0.05）;hsa-miR-31-5p was negatively correlated with AI,RF,IL-17,and positively correlated with IL-10（P < 0.05）;hsa-miR-29c-3p was negatively correlated with RF and IL-11（P < 0.05）;and there was a negative correlation between hsa-miR-3184-5p and IL-4（P < 0.05）.Conclusion:There are hsa-miRNAs differentially expressed in PBMCs of AA rats,which are significantly correlated with immune inflammatory indicators.XFC can improve both immune inflammatory indicators and miRNAs,and its mechanism needs further study.

　　【Keywords】 rheumatoid arthritis;adjuvant arthritis;micro RNAs;Xinfeng Capsule（新风胶囊）;intervention study;rats