摘要
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。
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.
作者
钱飞亚
杨培
张明菲
许阿兰
王祥
周学平
黄艳
周玲玲
QIAN Fei-ya;YANG Pei;ZHANG Ming-fei;XU A-lan;WANG Xiang;ZHOU Xue-ping;HUANG Yan;ZHOU Ling-ling(School of Pharmacy,Nanjing University of Chinese Medicine,Jiangsu Provincial Key Lab ofPharmacology and Safety Evaluation of Materia Medica,Nanjing210023,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2019年第5期720-726,共7页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81673937
81573869
81573929)
江苏省青年自然科学基金资助项目(No BK20161043)
