青蒿琥酯的免疫抑制作用及其机制研究  

Immunosuppressive and Regulatory Mechanism of Artesunate

作　　者：梅昕[1] 刘婧[1] 白玫[1] 吴可柱[1] 蒋云根[1] 

机构地区：[1]武警江西总队医院药剂科,南昌330001

出　　处：《中国药学杂志》2013年第11期878-883,841,共6页Chinese Pharmaceutical Journal

基　　金：国家科技部重大创新支撑项目(2011ZXJ109105-08B);中国博士后科学基金面上项目(20090461498);天津市自然科学基金面上项目(08JCYBJC070000);天津市应用基础与前沿技术研究计划(11JCYBJC14600)

摘　　要：目的初步研究青蒿琥酯体内外发挥免疫抑制的机制。方法体外研究观察青蒿琥酯对小鼠淋巴细胞毒性及对细胞增殖的影响。通过迟发型超敏反应小鼠模型研究青蒿琥酯在体内的免疫效应;采用逆转录一聚合酶链反应与酶联免疫吸附法检测Treg/Th17细胞特异性核因子及相关细胞因子的表达与含量;蛋白质印迹法检测p38丝裂酶原激活蛋白激酶蛋白的表达水平。结果青蒿琥酯明显抑制刀豆蛋白A及脂多糖诱导的淋巴细胞增殖;与地塞米松相比毒性更低。体内给药后,青蒿琥酯能减轻迟发型超敏反应小鼠耳肿胀;上调Foxp3及白细胞介素-10表达量,下调ROR-γt与白细胞介素17水平;抑制p38丝裂酶原激活蛋白激酶的磷酸化活性。结论青蒿琥酯可能通过其抗炎及调节Treg/Th17平衡而发挥免疫抑制作用,是一种新型免疫调节剂。OBJECTIVE To determine the immunoregulatory znechanism of artesunate both in vitro and in vivo. METHODS The immunosuppressive action of artesunate was investigated through lymphocyte proliferation amd cytotoxicity was also detected in vitro. The delayed-type hypensensitivity （DTH） mcxtel in mice was used for the investigation of artesunate in vivo. The nuqNA expression of T-bet, GATA-3, ROR-γt and IL-17 gene was determined by RT-PCR. ELISA assay was used to detect the contents of IL-17, and Western blot assay was applied to investigate the p38 mitogen-activated protein kinase （MAPK） activation. RESULTS Artesunate could inhibit ConA-induced T lymphocyte and LPS-induced B lymphocyte proliferation in vitro significantly, which also showed lower toxicity than dexamethasone. Mean- while, topical application of artesunate could both suppress the increase on ear thickness in DTH mice and inhibit the thymus index and spleen index. Furthermore, artesunate was found to regulate the expression level of transcription factor （T-bet in the GATA-3）, and down-regulate ROR-γt and IL-17 expression. What＇s more, the production of IL-17 was decreased in ear tissue. Finally, artesunate was observed to decrease p38 mitogen-activated protein kinase （MAPK） activation. CONCLUSION Artesunate, as a new immunomodulatory agents, might contribute to performing immunosuppression through modulating the balance of treg/Th17 and anti-inflammatory.

关 键 词：青蒿琥酯 免疫抑制 迟发型超敏反应 TREG TH17 p38丝裂酶原激活蛋白激酶 

分 类 号：R965[医药卫生—药理学]