Drp-1基因在高糖诱导胰岛β细胞凋亡中的作用  

The effect of dynamin-related protein 1 on high glucose-induced pancreatic β cell apoptosis

作　　者：门秀丽[1] 许世清[2] 徐梅[2] 张文健[2] 徐亚平[2] 叶丽亚[2] 娄晋宁[2] 

机构地区：[1]河北联合大学基础医学院病理生理学教研室,唐山063000 [2]卫生部中日友好医院临床医学研究所

出　　处：《中国糖尿病杂志》2012年第2期141-143,共3页Chinese Journal of Diabetes

基　　金：国家基础研究计划项目(2006CB503906);国家自然科学基金资助项目(30971410)

摘　　要：目的探讨动力相关蛋白-1(Drp-1)基因表达对高糖诱导胰岛β细胞凋亡的影响。方法高糖条件下,观察可诱导表达野生型Drp-1(Drp-1WT)基因和突变型Drp-1(Drp-1K38A)基因的大鼠胰岛β细胞凋亡情况。结果强力土霉素(Dox)可诱导胰岛β细胞Drp-1基因表达,并且Drp-1的表达与Dox之间存在明显的剂量和时间依赖关系。在高糖条件下,Drp-1WT基因高表达细胞的凋亡明显增多(39.1%),而Drp-1K38A高表达细胞的凋亡未见明显增加(8.9%)。并且高糖条件下,Dox诱导后的Drp-1WT细胞中可见线粒体分裂和细胞色素c释放,细胞中caspase 3活性升高,ROS产生增加,而这些变化在高表达Drp-1K38A的细胞中不明显。结论 Drp-1基因参与高糖诱导的胰岛β细胞凋亡。Objective To explore the effect of dynamin-related protein 1（Drp-1） on high glucose-induced β cell apoptosis. Methods The inducible expression of either wild-type Drp-1（Drp-1WT） or its dominant-negative mutant （Drp-1K38A） in β cell lines were used to investigate the effects of expression of Drp-1 on high glucose-induced pancreatic β cell apoptosis and to probe the mechanisms of apoptosis. Results Both Drp-1WT and Drp-1K38A proteins of β cell lines were induced by doxycycline in dose and time dependent manner.In response to high glucose,the apoptosis was increased in Drp-1WT cells（39.1%）,but not in Drp-1K38A cells（8.9%） after induction of Dox（P〈0.05）.Glucose-evoked mitochondrial fission,release of cytochrome C,the increase of the activity of caspase3 and generation of ROS were found in Drp-1WT cells,but not in Drp-1K38A cells after Dox induction. Conclusion Drp-1 is implicated in β cell glucotoxicity and apoptosis.

关 键 词：动力相关蛋白-1 胰岛Β细胞 凋亡 线粒体分裂 

分 类 号：R363[医药卫生—病理学]