滋肾通络方对胶原性关节炎小鼠Th17/Treg细胞分化及平衡的影响

目的观察滋肾通络方(ZTF)对胶原性关节炎(CIA)小鼠Th17/Treg细胞分化平衡的影响,探讨其治疗类风湿关节炎的机制。方法 DBA/1小鼠随机分为正常对照组、模型组和ZTF组(8.4 g生药·kg^-1),造模21 d后每日灌胃给药,连续4周。检测关节炎指数、关节病理改变、血浆IL-10和IL-17水平、外周血和脾脏Th17/Treg细胞比例、CD4^+T细胞IL-10、IL-17 mRNA水平。结果 CIA小鼠踝关节病变明显,血浆IL-17水平、外周血和脾脏Th17细胞比例、CD4^+T细胞IL-17 mRNA表达明显升高;血浆IL-10水平、外周血和脾脏Treg细胞比例、CD4^+T细胞IL-10 mRNA表达明显降低。ZTF能明显减轻CIA小鼠关节病变,降低血浆IL-17水平、外周血和脾脏Th17细胞比例、CD4^+T细胞IL-17 mRNA表达;升高血浆IL-10水平、外周血和脾脏Treg细胞比例、CD4^+T细胞IL-10 mRNA水平。结论 CIA小鼠存在Th17/Treg细胞失平衡,ZTF可调节Th17/Treg细胞比例,重构Th17/Treg细胞平衡,调节相关细胞因子释放,这可能是ZTF治疗类风湿关节炎的机制之一。

Effect of ZishenTongluo formula on differentiation and balance of Th17/Treg cells in collagen-induced arthritis

Aim To explore the effect of ZishenTongluo formula (ZTF) on the differentiation and the balance of Th17/Treg cells in collagen-induced arthritis (CIA) and its mechanisms. Methods DBA/1 mice were used to induce the arthritis model through injecting collagen Ⅱ,and they were randomly divided into the model group and ZTF group (8.4 g·kg-1 ) 21 days later.Another DBA/1 mice were used as control.General conditions and joint swelling were observed.After four weeks of administration,the histopathologic changes of ankle tissues,the levels of IL-10 and IL-17 in plasma,the ratio of Th17 and Treg cells in peripheral blood and spleen,and the expression of IL-10 and IL-17 mRNA in CD4+ T cells were measured. Results CIA mice showed significant joint swelling.The levels of IL-17 in plasma of CIA mice significantly increased and the levels of IL-10 significantly decreased.The proportion of Th17 cells in blood and spleen,and the expression of IL-17 mRNA in CD4+ T cells increased significantly,while the proportion of Treg cells and the expression of IL-10 mRNA decreased significantly in CIA mice.After treating with ZTF,the joint swelling and arthritis scores were obviously reduced,the levels of IL-17 in plasma decreased and the levels of IL-10 increased.Meanwhile,the proportion of Th17 cells in blood and spleen,and the expression of IL-17 mRNA in CD4+ T cells decreased,while the proportion of Treg cells and the expression of IL-10 mRNA increased. Conclusions Th17/Treg cell imbalance exists in CIA mice.ZTF could regulate the ratio of Th17 and Treg cells,resume the Th17/Treg balance,and then regulate the release of related cytokines.That may be one of the mechanisms of ZTF in treating rheumatoid arthritis.