中国中西医结合杂志2025，Vol.45Issue(4)：440-446,7.DOI:10.7661/j.cjim.20241220.276
二仙丸加减方对胶原诱导型关节炎大鼠关节炎症反应的影响
Effects of Modified Erxian Pill on Joint Inflammation in Collagen-induced Arthritis Rats
摘要
Abstract
Objective To study the effect of Modified Erxian Pill on collagen-induced arthritis(CIA)rats,and to observe its effect on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase(Caspase-1)/gasdermin D(GSDMD)pyroptosis signaling pathway.Methods Totally 24 Wistar female rats were randomly divided into normal control group,model group and Modified Erxian Pill group,8 in each group.Except the normal control group,the CIA rat model was constructed with bovine type Ⅱ collagen,Freund's complete adjuvant,and Freund's incomplete adjuvant in the other two groups.After the successful modeling,rats in Modified Erxian Pill group were administered with Modified Erxian Pill by gastrogavage(0.9 g/kg body weight).Equal volume of normal saline was administered to rats in the normal control group and the model group by gastrogavage.The gastrogavage was lasted for 4 successive weeks.The arthritis score,the diameter of ankle joint,the total distance of autonomous movement,and the histological changes of ankle joint were measured.The core target of Modified Erxian Pill in the treatment of rheumatoid arthritis(RA)was analyzed by network pharmacology.And the protein expression levels of NLRP3,Caspase-1,GSDMD,Gasdermin D-N(GSDMD-N),interleukin-1 β(IL-1 β)and interleukin-18(IL-18)in ankle tissues of rats in each group were detected by Western Blot.Results Compared with the normal control group,arthritis score and ankle joint diameter of CIA model rats significantly increased(P＜0.05),total distance of autonomic movement was significantly reduced(P＜0.05),joint space was narrowed,synovial hyperplasia was obviously seen,and a large number of inflammatory cell infiltration and bone destruction were observed.After 4 weeks of treatment,as compared with the model group,arthritis score and ankle joint diameter of rats in Modified Erxian Pill group were significantly lower than those in model group(P＜0.05),total distance of autonomous movement significantly increased(P＜0.05),and joint inflammation was significantly attenuated.The analyses of network pharmacology showed that the core target of Modified Erxian Pill for RA was IL-1 β.Meanwhile,the expression levels of IL-1 β and its upstream and downstream target proteins(including NLRP3,Caspase-1,GSDMD,GSDMD-N,and IL-18)in ankle tissues of the model group were significantly higher than those of the normal control group(P＜0.05).The expression levels of related proteins significantly decreased after Modified Erxian Pill treatment(P＜0.05).Conclusion Modified Erxian Pill improved IL-1 β-mediated joint inflammation in CIA rats possibly by inhibiting the activities of NLRP3/Caspase-1/GSDMD pyroptosis pathways.关键词
二仙丸加减方/胶原诱导性关节炎/细胞焦亡/白细胞介素-1β/类风湿关节炎/中药复方Key words
Modified Erxian Pill/collagen-induced arthritis/pyroptosis/interleukin-1 β/rheumatoid arthritis/Chinese herbal compound引用本文复制引用
李思源,徐烨,王瑜茹,南楠,刘杨,郝慧琴..二仙丸加减方对胶原诱导型关节炎大鼠关节炎症反应的影响[J].中国中西医结合杂志,2025,45(4):440-446,7.基金项目
中央引导地方科技发展资金项目(No.YDZJSX2021A040) （No.YDZJSX2021A040）
中西医结合防治风湿免疫病山西省科技创新人才重点团队项目(No.202204051002033) （No.202204051002033）
山西中医药大学风湿免疫性疾病中西医结合基础学科建设项目(No.2023XKJS-03) （No.2023XKJS-03）
经方扶阳山西省重点实验室开放课题研究基金资助项目(No.202104010910011) （No.202104010910011）
山西中医药大学2022年研究生教育创新项目(No.2022CX014) （No.2022CX014）
