人参皂苷衍生物AD-1对CD4^(+)T细胞亚群的调控及对DSS诱导的实验性结肠炎小鼠的影响

Regulation of Ginsenoside derivative AD-1 on CD4^(+)T cell subsets and its effect on DSS-induced experimental colitis mice

目的:探讨新型人参皂苷衍生物AD-1对体外分化CD4^(+)T细胞亚群的影响及对DSS诱导的实验性结肠炎小鼠CD4^(+)T细胞亚群的调控作用。方法:采用磁珠阴性选择法获得正常小鼠幼稚CD4^(+)T细胞,定向分化为Th1、Th2、Th17细胞、Treg,流式细胞术检测AD-1对其分化的影响。3%DSS三次循环法建立小鼠实验性结肠炎模型,AD-1药物干预后,流式细胞术、HE染色检测结肠、脾脏、肠系膜淋巴结中Th1、Th2、Th17细胞、Treg所分泌的细胞因子和特异性转录因子。结果:细胞活化后,早期标志物CD69无显著变化;AD-1下调Th1和Th17细胞分泌的细胞因子IFN-γ和IL-17A表达,上调Th2细胞分泌的细胞因子IL-4和Treg转录因子Foxp3及表面标志物CD25表达。AD-1可通过下调脾脏和肠系膜淋巴结中Th1和Th17细胞表达及上调Th2和Treg表达改善DSS诱导的小鼠实验性结肠炎。结论:AD-1对CD4^(+)T细胞活化无影响,但可抑制Th1和Th17细胞分化,促进Th2细胞和Treg分化,同时通过调节CD4^(+)T细胞亚群改善DSS诱导的小鼠实验性结肠炎。

Objective:To investigate effect of a new ginsenoside derivative AD-1 on differentiation of CD4^(+)T cell subsets in vitro and regulation of CD4^(+)T cell subsets in DSS-induced experimental colitis mice.Methods:Magnetic bead negative selection method was used to obtain naive CD4^(+)T cells from normal mice and differentiated into Th1,Th2,Th17 cells and Treg,and flow cytometry was used to detect effect of AD-1 on their differentiation. 3%DSS three-cycle method was used to establish an experimental colitis mouse model. After intervention of AD-1 drugs,flow cytometry and HE staining were used to detect cytokines and specific transcription secreted by Th1,Th2,Th17 cells and Treg in colon,spleen and mesenteric lymph nodes were tested.Results:After cell activation,early marker CD69 did not change significantly;AD-1 down-regulated expressions of cytokines IFN-γ and IL-17A secreted by Th1 and Th17 cells,and up-regulated expressions of cytokine IL-4 secreted by Th2 cells and Treg transcription factor Foxp3 and surface marker CD25. AD-1 improved experimental colitis induced by DSS in mice by down-regulating expressions of Th1 and Th17 cells in spleen and mesenteric lymph nodes and up-regulating expression of Th2 cells and Treg.Conclusion:AD-1 has no effect on activation of CD4^(+)T cells,however can inhibit differentiation of Th1 and Th17 cells and promote differentiation of Th2 cells and Treg,and can improve experimental colitis induced by DSS in mice by regulating CD4^(+)T cell subsets at the same time.