线粒体功能障碍在胰岛β细胞脂性凋亡中的作用  

Mechanism of lipotoxicity-associated apoptosis mediated by mitochondrial dysfunction in pancreatic β-cells

作　　者：王威[1,2] 张丹[1] 陈颖[1] 曹翠萍[1] 韩玲玲[1] 刘国良[1] 

机构地区：[1]中国医科大学附属第一医院内分泌科,辽宁沈阳110001 [2]哈尔滨医科大学附属第二医院内分泌科,黑龙江哈尔滨150086

出　　处：《中国病理生理杂志》2010年第1期163-166,共4页Chinese Journal of Pathophysiology

摘　　要：目的:探讨线粒体途径在脂毒性诱导的胰岛β细胞株MIN6凋亡中的作用。方法:胰岛β细胞株MIN6分别在含或不含棕榈酸(0.1-0.5mmol/L)的DMEM无血浆培养基中孵育24h;Hoechst33258染色法检测细胞凋亡,用试剂盒测定caspase-3活性;透射电镜观察MIN6细胞株线粒体结构;RT-PCR法检测bcl-2相关X蛋白(bax)、B细胞淋巴瘤因子2(bcl-2)、固醇调节元件结合蛋白亚型1c(SREBP1c)和DNA损伤可诱导的转录子3(chop-10)mRNA的表达。结果:棕榈酸诱导MIN6细胞凋亡,引起细胞线粒体肿胀,抑制bcl-2mRNA的表达并促进bax、SREBP1c和chop-10mRNA的表达。结论:棕榈酸通过促进线粒体功能障碍而诱导胰岛β细胞凋亡,这一过程可能和bax、bcl-2、SREBP1c和chop-10mRNA表达异常有关。AIM ： To investigate the mechanism of lipotoxicity - associated apoptosis mediated by mitochondrial pathway in pancreatic β-cells. METHODS： The pancreatic β-cell line MIN6 cells were incubated respectively in serum- free DMEM medium with or without palmitate （0.1 -0.5 mmol/L） for 24 h, followed by Hoechst 33258 staining. The activity of caspase 3 was assayed for determining apoptosis, transmission electron microscope was used for observing mitochondrial structure, and RT - PCR analysis was applied for detection of mRNA expression of bcl - 2 - associated X protein （ bax）, B - celt lymphoma 2 （ bcl - 2 ）, sterol regulatory element binding transcription factor 1c （SREBP1c） and DNA -damage inducible transcript 3 （chop - 10）. RESULTS： Palmitate induced apoptosis of MIN6 cells and swelling of mitochondria. Palmitate also inhibited mRNA expression of bcl- 2, whereas enhanced mRNA expression of bax, SREBP1 c and chop- 10. CONCLUSION： Palmitate induces apoptosis of pancreatic β- cells by promoting mitochondrial dysfunction, which is associated with abnormal expressions of bax, bcl-2, SREBP1c and chop- 10.

关 键 词：线粒体 MIN6细胞 细胞凋亡 

分 类 号：R363[医药卫生—病理学]