SP600125抑制FFA诱导的肝星状细胞凋亡及可能机制  

JNK inhibitor SP600125 suppresses free fatty acid-induced apoptosis of hepatic stellate cells

作　　者：王珣 王明林 鲁新耀 张鹏 于红刚[2] 胡义奎[3] 

机构地区：[1]武汉市武昌医院消化内科,湖北省武汉市430063 [2]武汉大学人民医院消化内科,湖北省武汉市430060 [3]华中科技大学同济医学院附属普爱医院神经内科,湖北省武汉市430034

出　　处：《世界华人消化杂志》2014年第23期3435-3439,共5页World Chinese Journal of Digestology

基　　金：武汉市卫生局科研基金资助项目;No.WX1321~~

摘　　要：目的:探讨c-Jun氨基末端激酶(c-Jun N-terminal kinase)抑制剂-SP600125在游离脂肪酸(free fatty acids,FFA)诱导的肝星状细胞(hepatic stellate cell,HSC)凋亡中的作用.方法:采用MTT比色法检测FFA对HSC细胞生长的抑制作用;流式细胞技术(flow cytometry,FCM)检测HSC细胞凋亡率;蛋白质印迹(Western blot)法检测p-JNK、p-c-Jun蛋白表达,比较在FFA作用下及SP600125阻断JNK信号通路情况下上述蛋白的表达水平.结果:与对照组比较,FFA可诱导HSC细胞凋亡,差异具有统计学意义(P<0.05);FFA诱导HSC细胞凋亡过程中,p-JNK和p-c-Jun蛋白显著增加(P<0.05);用SP600125预处理HSC细胞后,p-JNK和p-c-Jun蛋白含量较未处理组明显减少(P<0.05).结论:FFA可诱导HSC细胞凋亡;凋亡过程可能系通过JNK通路实现;JNK抑制剂-SP600125可能通过抑制JNK通路阻止HSC细胞凋亡,有望成为治疗非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)的新型药物.AIM： To elucidate the potential effects of c-Jun amino terminal kinase（JNK） inhibitor SP600125 on apoptosis induced by free fatty acids（FFAs） in hepatic stellate cells and the possible mechanism.METHODS： MTT assay was used to analyze theinhibitory effect of FFAs on growth of hepaticstellate cells,and flow cytometry was used to observe the apoptotic rate of the cells.The expres-sion of p-JNK and p-c-Jun proteins was detected by Western blot assay.RESULTS： The growth of hepatic stellate cells was significantly inhibited by FFAs in vitro,and FFAs increased the expression of p-JNK and p-c-Jun.JNK inhibitor SP600125 suppressed FFA-induced up-regulation of p-JNK and p-c-Jun.CONCLUSION： FFAs can inhibit the prolif-eration of hepatic stellate cells and induce cell apoptosis,which involves the JNK signaling pathway.

关 键 词：非酒精性脂肪性肝炎 游离脂肪酸 肝星状细胞 C-JUN氨基末端激酶 凋亡 

分 类 号：R575.5[医药卫生—消化系统]