青蒿琥酯通过上调神经酰胺抑制肝星状细胞增殖并诱导其凋亡  

Artesunate inhibits the proliferation of hepatic stellate cells and induces apoptosis by upregulating ceramide

作　　者：马淑晶 张晓燕[1] 徐亚洁[1] 方步武[1] 

机构地区：[1]天津医科大学药理学教研室,天津300070

出　　处：《天津医科大学学报》2014年第4期253-256,共4页Journal of Tianjin Medical University

基　　金：国家自然科学基金资助项目(30772856)

摘　　要：目的:探讨神经酰胺与青蒿琥酯抗肝纤维化作用的关系。方法:将培养的肝星状细胞分为实验组和对照组,实验组为不同浓度的青蒿琥酯处理组及神经酰胺处理组。以四甲基偶氮唑盐(MTT)法检测肝星状细胞(HSC)增殖率,Hoechst 33258荧光染色观察细胞凋亡,Annexin V-FITC/PI双染检测细胞凋亡率,HPLC-FLD法测定青蒿琥酯处理后HSC培养上清中的神经酰胺的含量,均数比较采用单因素方差分析,两样本均数比较采用独立样本t检验。结果:不同浓度青蒿琥酯及神经酰胺对肝星状细胞均有明显抑制作用,且呈剂量-效应关系和时间-效应关系(P<0.01),青蒿琥酯及神经酰胺均能诱导肝星状细胞的凋亡,青蒿琥酯能够上调细胞培养上清液中神经酰胺的含量。结论:青蒿琥酯可能通过上调神经酰胺抑制肝星状细胞的增殖并诱导其凋亡。Objective： To investigate the relationship between ceramide and artesunate on antifibrotic effect. Methods： The cultured hepatic stellate cells were divided into experimental group and control group, with the former including different concentrations of artesunate-treated groups and ceramide-treated groups. Cell proliferation rate was measured using the 3-（4, 5-dimethyhhiazol-2-yl）-2, 5- diphenyherazolium bromide （MTT）, cell apoptosis was observed by Hoechst 33258 taining, and the cell apoptosis rate was detected by AnnexinV-FITC/PI double staining while the content of ceramide （C2） in HSCs treated with artesunate was evaluated by HPLC-FLD. The means were compared using ANOVA and the two samples were compared using independent sample t test. Results： Different concentrations of artesunate and ceramide on hepatic stellate cells were significantly reduced in a dose-response and time-effect relationship （P〈0.01）, artesunate and ceramide could induce apoptosis in hepatic stellate cells and artesunate could increase the content of ceramide in the cell culture supematant. Conclusion： Artesunate could inhibit the proliferation and induce apoptosis of hepatic stellate cells through upregulating ceramide.

关 键 词：青蒿琥酯 神经酰胺 肝星状细胞 增殖 凋亡 

分 类 号：R96[医药卫生—药理学]