雷公藤甲素、红素可溶性微针抗类风湿性关节炎的药效研究

Pharmacodynamic study on the efficacy of Triptolide and Celastrol soluble Microneedle against rheumatoid arthritis

目的:探讨雷公藤甲素、红素可溶性微针(TP-Cel-DMN)治疗类风湿性关节炎(RA)的作用。方法:基于网络药理学和分子对接技术预测雷公藤甲素(TP)、雷公藤红素(Cel)抗RA的核心靶点。30只雄性SD大鼠分为空白组、模型组、空白微针组、扶他林组、TP-Cel-DMN组,每组6只。除空白组外,其余各组构建佐剂性关节炎大鼠模型。造模成功后,各给药组持续28d给予相应的治疗。给药结束后,测定大鼠足跖肿胀度,胸腺、脾脏指数;HE染色观察踝关节滑膜组织的病理学变化;ELISA法测定血清中核心靶点的表达。结果:TP、Cel抗RA的核心靶点为IL6、TNF、VEGFA。药效实验显示,第21、28天,与模型组比较,TP-Cel-DMN组可显著降低大鼠足跖肿胀度(P<0.01),改善踝关节滑膜病理状态;降低胸腺指数(P<0.05)和血清中IL-6、TNF-α、VECF-A含量(P<0.01)。结论:TP-Cel-DMN可有效抗RA,该结果可为TP-Cel-DMN的运用提供实验依据。

Objective:To investigate the effects of Triptolide,Celastrol soluble Microneedle(TP,Cel-DMN)in the treatment of rheumatoid arthritis(RA).Methods:Based on network pharmacology and molecular docking technology to screen out the core targets of Triptolide and Celastrol against RA.Thirty male rats were divided into blank group,model group,positive drug Voltaren group,TP,Cel-DMN group and blank Microneedle group,with 6 rats in each group.Except the blank group,the adjuvant arthritis rat model was constructed in other groups.After successful modeling,each administration group was given corresponding treatment for 28 days.After administration,the swelling of the toes,the indexes of thymus and spleen were measured;the ankle joint synovial tissue was stained with HE to observe the pathological changes;the expression of core targets in serum was measured by ELISA.Results:The core targets of Triptolide and Celastrol against RA were IL6,TNF,and VEGFA.Pharmacodynamic experiments showed that,after treatment with TP,Cel-DMN,compared with the model group,it could significantly reduce the swelling of the toes of the rats(P<0.01)on the 21st and 28th day;improve the pathological state of the ankle joint synovium;reduce thymus index(P<0.05)and serum IL-6,TNF-α,VEGF-A levels(P<0.01).Conclusion:TP,Cel-DMN can effectively resist RA.This result can provide experimental basis for the application of TP-Cel-DMN.