目的 以“肠-关节”轴为切入点，探讨金藤清痹颗粒抗类风湿关节炎的作用机制。方法 按体质量将大鼠随机分为6组，即对照组、模型组、双氯芬酸钠组以及金藤清痹颗粒高、中、低剂量组，每组6只。采用胶原诱导法进行造模，设计金藤清痹颗粒高、中、低剂量组给药剂量分别为6.30、3.15、1.58 g/kg；双氯芬酸钠组给药剂量为3 mg/kg；对照组和模型组ig等量生理盐水，给药4周。苏木精-伊红染色法（HE）观察大鼠踝关节部位病理变化，酶联免疫吸附测定法（ELISA）检测大鼠血清相关炎症指标，16S rDNA分析盲肠内容物中肠道菌群变化。结果 与模型组比较，金藤清痹颗粒可明显降低胶原诱导型关节炎模型大鼠关节肿胀度，减少踝关节炎性细胞浸润，同时可显著降低胶原诱导型关节炎大鼠血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、C反应蛋白（CRP）水平（P＜0.05、0.01）；16S rDNA结果显示，金藤清痹颗粒6.30 g/kg可增加Cyanobacteria、软壁菌门、疣微菌门、梭杆菌门、毛螺菌科NK4A136群和Ruminiclostridium 5等菌群的相对丰度，以及降低变形菌门、乳杆菌属和瘤胃球菌属1等菌群的相对丰度。结论 金藤清痹颗粒可能通过调控“肠-关节”轴发挥抗类风湿关节炎的作用。

Objective To tnvestigated the mechanism of Jinteng Qingbi Granules against rheumatoid arthritis based on gut microbiota. Methods According to body weight, the rats were randomly divided into 6 groups, namely control group, model group, diclofenac sodium group, and Jinteng Qingbi Granules high, medium, and low-dose groups, with 6 rats in each group. Collagen induction method was used for modeling, and the dosages of Jinteng Qingbi Granules in high, medium, and low dose groups were 6.30, 3.15,1.58 g/kg, respectively. The dose of diclofenac sodium group was 3 mg/kg; Control group and model group were given the same amount of normal saline intragastrically for 4 weeks. Hematoxylin-eosin staining (HE) was used to observe the pathological changes of the ankle joint of the rats, ELISA was used to detect the serum inflammatory indicators, and 16S rDNA was used to analyze the changes of intestinal flora in the cecum contents. Results Compared with the model group, Jinteng Qingbi Granules could significantly reduce the degree of joint swelling, the infiltration of ankle arthritic cells, and the serum levels of TNF-α, IL-1β and CRP in collagen-induced arthritis model rats. At the same time, 16S rDNA showed that Jinteng Qingbi Granules could increase the relative abundance of Cyanobacteria, Tenericutes, Verrucomicrobia, Fusobacteria, Lachnospiraceae NK4A136 group, and Ruminiclostridium 5, as well as decrease the relative abundance of Proteobacteria, Lactobacillus and Ruminococcus 1. Conclusion Jinteng Qingbi Granules may play an anti-rheumatoid arthritis role by regulating the “gut-joint” axis.

R979.5

河南省医学科技攻关计划联合共建项目（LHGJ20190275）