雷公藤甲素与双氢青蒿素配伍对大鼠佐剂性关节炎的免疫学研究

Study on the Immunology of Triptolide and Dihydroartemisinine Compound Treating AA Rats

目的:从病理及免疫学的角度观察小剂量的雷公藤甲素与双氢青蒿素配伍对大鼠佐剂性关节炎的影响,探讨能否通过减少雷公藤甲素的用量而降低药物的毒性。方法:将70只雄性SD大鼠随机分为7组(即正常组,模型组,雷公藤甲素高、低剂量组,雷公藤甲素双氢青蒿素高、中、低剂量组)。动物模型用弗氏完全佐剂于SD大鼠右后足跖皮内诱导关节炎发生。给药组治疗1个月后取血并处死动物,取关节进行病理学分析,并运用流式细胞术检测外周血T淋巴细胞亚群、免疫组化染色法检测踝关节软骨上的IL-6、TNF-α的表达。结果:与模型组相比,雷公藤甲素双氢青蒿素配伍可明显抑制AA大鼠的关节病理损伤,能显著降低外周血CD4+、CD4+/CD8+水平及降低踝关节软骨上的IL-6、TNF-α的表达(P<0.01),且与雷公藤甲素高剂量组比较则无差异(P>0.05),优于雷公藤甲素低剂量组(P<0.05)。结论:通过与双氢青蒿素配伍可以减少雷公藤甲素的用量。

Objective ：The present study was to explore the effect and the therapeutic mechanism of low dose triptolide and dihydroartemisinine compound on adjuvant-induced arthritis （AA） in rats from the pathological,immunological aspects. Through the study we explore the methods of decreasing triptolide, s toxicity. Methods ： 70 male SD rats were randomly divided into 7 groups （ normal group, model group, triptolide high dose group, triptolide low dose group, triptolide and dihydroarte- misinine compound high dose group, dihydroartemisinine compound middle dose group triptolide and dihydroartemisine compatibility low dose group）. Rheumatoid arthritis was induced by Freund＇ s complete adjuvant （CFA） injected into right postpedes in rats. The rats in the model group and normal group were fed with physiological saline, and triptolide groups were fed with triptolide,and triptolide and dihydroartemisine compound groups were fed with triptolide and dihydroartemisine compound. After a month, all rats were being execute. The changes of T cell subsets in the serum were assayed by FACA Calibur flow cytometer. TNF-α, IL-6 levels in s cartilage of SD rats were detected with Immunohistochemical method. The pathological change of the knee and ankle joints of SD rats were detected by telescope. Results ： Triptolide and dihydroarte- misinine compound can significantly improve arthritis degradation. Compared with the AA model group, CD4^＋ lymphocytes, the ratio of CD4^＋/CD8^＋ and the levels of TNF-α,IL-6 in cartilage of the compound groups were decreased. The effect of triptolide and dihydroarte- misinine high dose group slightly surpasses Triptolide low dose group, and is similar to triptolide high dose group. Conclusion：through compound dihydroartemisinine we can decrease the dose of triptolide