青蒿素的免疫抑制作用及其调控机制研究

The immunosuppressive and regulatory mechanism of artemisinin

目的初步探讨青蒿素(artemisinin,Art)体内外发挥免疫抑制作用的调控机制。方法体外研究检测Art对小鼠淋巴细胞增殖及细胞毒性的影响。体内研究中,通过迟发型超敏反应(delayed-type hypersensitivity,DTH)小鼠模型,分析不同剂量Art对小鼠DTH的效应;RT-PCR技术检测Th1和Th2细胞转录因子T-bet及GATA-3的基因表达;ELISA法检测转化生长因子β1(transforming growth factorβ1,TGF-β1)的含量;Western blot方法检测p38丝裂酶原激活蛋白激酶(p38 MAPK)蛋白的活性表达水平。结果 Art明显抑制刀豆蛋白A(concanavalin A,ConA)诱导的T淋巴细胞增殖;与地塞米松相比,具有更高的安全性。体内给药后,Art能够减轻DTH小鼠耳肿胀;降低小鼠的脾指数和胸腺指数;调节Th1/Th2细胞分化过程中特异性转录因子T-bet和GATA-3的mRNA表达水平;增加TGF-β1水平;抑制p38 MAPK的磷酸化活性表达。结论提取自传统中草药的Art是一种高效低毒的新型免疫调节剂,通过多种途径发挥免疫抑制作用。

Aim To determine the immunoregulatory mechanism of artemisinin both in vitro and in vivo.Methods The immunosuppressive action of artemisinin was investigated through lymphocyte proliferation in vitro.The delayed-type hypersensitivity（DTH） model in mice was used for the investigation of artemisinin in vivo.ELISA asssy was used to detect the contents of TGF-β1,and Western blot assay was applied to investigate the p38 mitogen-activated protein kinase（MAPK） activation.Besides,the mRNA expression of T-bet and GATA-3 gene was determined by RT-PCR.Results Artemisinin could inhibit concanavalin A-induced T lymphocyte proliferation in vitro significantly.Meanwhile,topical application of artemisinin could both suppress the increase on ear thickness in DTH mice and inhibit the thymus index and spleen index,whose security was better than dexamethasone.Furthermore,artemisinin was found to affect the gene expression shift of the specific transcription factor（T-bet and GATA-3） in Th1 and Th2 cell differentiation,and increase the production of TGF-β1.Finally,artemisinin was observed to decrease p38 mitogen-activated protein kinase（MAPK） activation.Conclusion Artemisinin,drived from traditional Chinese medicine,has immunosuppressive effect and can modulate immune response through multi-pathways.