二甲双胍对胰岛细胞脂毒性的保护作用  

Effects of metformin on lipotoxicitic apoptosis in mouse β Tc3 cells induced by free fatty acids

作　　者：王玉环[1] 达婷[1] 阎丽丽[1] 郑华东[1] 吴娟娟[1] 张静[1] 

机构地区：[1]西安交通大学医学院第二附属医院内分泌科,陕西西安710004

出　　处：《西安交通大学学报（医学版）》2009年第4期430-434,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省科技攻关项目(No .2003K10-G114);西安市科学技术局科技计划项目(No .SF08002)~~

摘　　要：目的探讨二甲双胍(MF)在游离脂肪酸(FFA)诱导的胰岛细胞凋亡中的作用及机制。方法采用四甲基偶氮唑蓝(MTT)比色法观察FFA对小鼠βTc3细胞增殖的抑制作用;流式细胞术检测细胞的凋亡率;免疫细胞化学和Western blot法检测p-JNK、p-c-jun在FFA、特异性JNK抑制剂(SP600125)阻断JNK信号转导通路情况下及MF作用下的表达。结果FFA对体外生长的βTc3细胞具有明显的抑制作用,并可诱导细胞凋亡;MF可显著减少这一过程中的细胞凋亡。细胞免疫化学及Western blot结果显示,FFA诱导βTc3细胞凋亡伴随着p-JNK和p-c-jun的升高而增加;用SP600125预处理βTc3细胞后,可以明显减少p-JNK和p-c-jun的活化,而MF没有能够抑制FFA引起的p-JNK活化。结论MF可以抑制FFA介导的小鼠βTc3细胞凋亡,但不是通过JNK信号转导通路发挥作用的。Objective To investigate the effects of meiformin on apoptosis in mouse β Tc3 cells induced by free fatty acids （FFA） and the underlying mechanism Methods MTT assay was used to observe the inhibitory actions of FFA on the proliferation of βTc3 cells. The apoptosis rate of the cells was detected by flow cytometry. The expressions of p-JNK and p-c-jun were detected by immunocytochemistry and Western blot. Results The proliferation of βTc3 cells was remarkably inhibited by FFA in vitro, and significant apoptosis was present. Metformin could inhibit the apoptosis significantly. Immunocytochemistry and Western blot results showed FFA induced activation of p-JNK, p-c-jun. As a JNK inhibitor, SP600125 partly suppressed FFA-induced activation of p-JNK and p-c-jun; however, metformin did not suppress it. Conclusion Metformin could inhibit the apoptosis of mouse βTc3 cells stimulated by free fatty acids, but the JNK signaling pathway is not involved in the mechanism.

关 键 词：游离脂肪酸 ΒTC3细胞 JNK信号通路 二甲双胍 脂性凋亡 

分 类 号：R587.1[医药卫生—内分泌]