栀子苷对类风湿性关节炎大鼠Th17/Treg平衡和局部炎症因子的影响

The Effects of Geniposide on Th17/Treg Balance and Local Inflammatory Factors in Rats with Rheumatoid Arthritis

目的考察栀子苷对类风湿性关节炎大鼠Th17/Treg平衡和局部炎症因子的影响。方法建立大鼠胶原诱导关节炎模型,通过病理切片观察踝关节组织变化,ELISA检测血清TNF-α,Western blot法检测转录因子Foxp3和ROR-γt的蛋白表达,免疫组化法检测关节滑膜组织IL-10、IL-17表达。结果模型组血清TNF-α、IL-17以及ROR-γt和关节滑膜IL-17表达较正常组显著升高(P<0.01),而模型组血清IL-10浓度以及Foxp3和关节滑膜IL-10表达较正常组显著降低(P<0.01),栀子苷中、高剂量组血清TNF-α、IL-17浓度以及ROR-γt和关节滑膜IL-17表达较模型组显著降低(P<0.05~0.01),而血清IL-10浓度、Foxp3和关节滑膜IL-10表达较模型组显著升高(P<0.05~0.01)。结论大鼠胶原诱导关节炎模型成模之后Treg/Th17会失衡,栀子苷可升高IL-10、Foxp3表达,降低IL-17、ROR-γt表达,提示其可能通过诱导Treg细胞生成同时抑制Th17细胞分化,从而恢复病变部位Treg/Th17的平衡。

OBJECTIVE To investigate the effects of geniposide on Th17/Treg balance and local inflammatory factors in rats with rheumatoid arthritis.METHODS We established the CIA model to observe the histopathological changes of ankle joints in rats.ELISA was used to detect plasma TNFα,and Western blot was used to detect the protein contents of transcription factor Foxp3 and RORγt.The expression of IL 10 and IL 17 in joint synovial tissue was detected by immunohistochemistry.RESULTS Compared with the normal control group,the serum concentration of TNFα,IL 17 and RORγt and the expression of IL 17 in joint synovial tissue were significantly higher in the model group(P<0.01),while the concentration of IL 10 and Foxp3 and the expression of IL 10 in joint synovial tissue decreased significantly in the model group(P<0.01).Compared with the model group,the serum concentration of TNFα,IL 17 and RORγt and the expression of IL 17 in joint synovial tissue were significantly lower in the middle and high dose groups of geniposide(P<0.05,P<0.01),while the concentration of IL 10 and Foxp3 and the expression of IL 10 in joint synovial tissue increased significantly in the middle and high dose groups of geniposide(P<0.05,P<0.01).CONCLUSION There was an imbalanced Treg/Th17 differentiation in the joint synovium of CIA rats.By inhibiting the differentiation of Th17 cells in joint synovium,geniposide might induce the generation of Treg cells and then restore the Treg/Th17 balance in the diseased area.