青蒿琥酯抑制肝纤维化的作用及其机制  

Effects of Artesunate on hepatic fibrosis and its mechanism

作　　者：杜岩[1] 李立楠[1] 方步武[1] 

机构地区：[1]天津医科大学基础医学院药理学教研室,天津300070

出　　处：《中国应用生理学杂志》2015年第1期14-17,共4页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金资助项目(30772856)

摘　　要：目的:探讨青蒿琥酯(Art)对人源肝星状细胞(LX-2)的作用。方法:样本为体外培养人源肝星状细胞,实验分为对照组及3个不同剂量的Art(250、350、450μmol/L)组。四甲基偶氮唑盐法(MTT)检测LX-2的增殖情况,HPLC-FLD法检测LX-2上清中神经酰胺的含量,酶消化法测定羟脯氨(Hyp)的含量,Western blot法检测PPAR-γ、p53、Caspase 3蛋白在各组中的表达。结果:与对照组比较,不同浓度青蒿琥酯组对肝星状细胞增殖均有明显抑制作用,且呈剂量-效应关系(P<0.01);青蒿琥酯可提高神经酰胺的含量(P<0.01),同时各给药组羟脯氨酸的含量明显下降(P<0.05,P<0.01);与对照组比较,青蒿琥酯组PPAR-γ、p53、Caspase 3蛋白的表达上调(P<0.01)。结论:青蒿琥酯可能是通过上调神经酰胺,发挥抑制肝星状细胞增殖、促进其凋亡的作用。Objective： To investigate the effects of Artesunate（ Art） on the LX-2 cell. Methods： The cultured hepatic stellate cells were divided into control group and Art-treated groups with 250,350,450 μmol / L. The rate of cellular proliferation was detected by MTT assay,the content of ceramide（ Cer） was determined by HPLC method,the content of hydroxyproline（ Hyp） was determined by enzyme digestion method,the expressions of PPAR-γ,p53 and Caspase 3 were detected by Western blot. Results： Compared with control group,LX-2 treated with Art were inhibited in a concentration-dependent manner（ P 〈0. 01）. Art could significantly increase the content of ceramide in LX-2（ P 〈0. 01）,and the content of Hyp was significantly decreased（ P〈 0. 05,P〈 0. 01）. The expressions of PPAR-γ,p53 and Caspase 3 were increased compared with that of control group（ P 〈0. 01）. Conclusion： Artesunate could inhibit the proliferation and induce apoptosis of hepatic stellate cells through upregulating ceramide.

关 键 词：青蒿琥酯 肝纤维化 神经酰胺 PPAR-Γ P53 CASPASE 3 

分 类 号：R337.2[医药卫生—人体生理学]