·糖尿病基础研究·

　　门秀丽 许世清 徐梅 张文健 徐亚平 叶丽亚 娄晋宁

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

　　作者单位：063000唐山，河北联合大学基础医学院病理生理学教研室(门秀丽);卫生部中日友好医院临床医学研究所(许世清、徐梅、张文健、徐亚平、叶丽亚、娄晋宁)

　　通讯作者：娄晋宁，E-mail:Lou.j@mail.com

　　【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。

　　【关键词】动力相关蛋白-1;胰岛β细胞;凋亡;线粒体分裂

　　doi:10.3969/j.issn.1006-6187.2012.02.016

　　The effect of dynamin-related protein 1 on high glucose-induced pancreatic β cell apoptosisMEN Xiu-li, XU Shi-qing, XU mei, et al.Department of Pathophysiology, College of Elementary Medicine, Hebei United University, Hebei Tangshan 063000, China

　　Corresponding author: LOU Jin-ning, E-mail: Lou.j@mail.com

　　【Abstract】ObjectiveTo explore the effect of dynamin-related protein 1(Drp-1) on high glucose-induced β cell apoptosis. MethodsThe 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. ResultsBoth 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. ConclusionDrp-1 is implicated in β cell glucotoxicity and apoptosis.

　　【Key words】Dynamin-related protein-1; β cell; Apoptosis; Mitochondrial fission