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动力相关蛋白1抑制剂减轻糖尿病小鼠心肌缺血/再灌注损伤

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第4期
页码:
378-382
栏目:
基础研究
出版日期:
2018-04-25

文章信息/Info

Title:
Inhibition of dynamin-related protein 1 reduces myocardial ischemia-reperfusion injury in diabetic mice
作者:
刘 铮1刘振华1贾 敏2冯嘉豪1李泽阳1丁铭格3付 锋2
(第四军医大学:1.学员一旅,2.基础医学院生理学教研室,陕西 西安 710032;3.西安市中心医院老年病科,陕西 西安 710003)
Author(s):
LIU Zheng1 LIU Zhen-hua1 JIA Min2 FENG Jia-hao1 LI Ze-yang1 DING Ming-ge3 FU Feng2
(1.First Cadet Brigade, 2.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China; 3.Department of Geriatrics, Xi’an Central Hospital, Xi’an 710003, Shaanxi, China)
关键词:
动力相关蛋白线粒体分裂糖尿病心肌缺血/再灌注氧化应激
Keywords:
dynamin-related protein 1 mitochondrial fission diabetesl myocardial ischemia-reperfusion oxidative stress
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的 探究动力相关蛋白(Dynamin-related protein,Drp)1抑制剂Mdivi-1对糖尿病小鼠心肌缺血/再灌注(Myocardial ischemia/reperfusion,MI/R)损伤的作用及其机制。方法 高脂饮食加小剂量链脲佐菌素(STZ)诱导建立糖尿病小鼠模型。造模成功的糖尿病小鼠进行MI/R处理,再灌注前15 min腹腔注射Mdivi-1(1.2 mg/kg)或其溶剂二甲基亚砜。主要评价指标包括线粒体形态、心脏功能、心肌损伤及凋亡,蛋白免疫印迹检测Drp1表达。结果 糖尿病MI/R后线粒体分裂增加(P<0.01),线粒体Drp1转位明显增加(P<0.01),Mdivi-1可抑制缺血/再灌注心肌的Drp1线粒体转位及线粒体分裂,减少心肌梗死面积和心肌细胞凋亡(P<0.01),减轻氧化应激(P<0.05)。结论 Drp1介导的线粒体分裂增加参与了糖尿病MI/R损伤,Drp1抑制剂Mdivi-1可抑制线粒体分裂,减轻糖尿病MI/R损伤。
Abstract:
AIM To investigate the effects of Mdivi-1, a small molecule inhibitor of dynamin-related protein 1 (Drp1), on myocardial ischemia-reperfusion injury in diabetic mice. METHODS High-fat diet and streptozotocin-induced diabetic mice were subjected to myocardial ischemia-reperfusion (MI/R) or sham operation. Mdivi-1 (1.2 mg/kg) or vehicle (dimethyl sulfoxide) was administrated to the mice 15 min before the onset of reperfusion by intraperitoneal injection. Outcome measures included mitochondrial morphology, cardiac functions, myocardial injury and apoptosis. The expression of Drp1 was analyzed by Western blot. RESULTS Enhanced mitochondrial fission and increased mitochondrial Drp1 translocation were induced by I/R in diabetic hearts. Delivery of Mdivi-1 into diabetic mice markedly inhibited Drp1 translocation to the mitochondria and reduced mitochondrial fission following MI/R. Inhibition of Drp1 reduced myocardial infarct size, inhibited cardiomyocyte apoptosis and alleviated oxidative stress in diabetic MI/R mice. CONCLUSION Drp1-mediated mitochondrial fission is involved in diabetic MI/R injury. Pharmacological inhibition of Drp1 with Mdivi-1 prevents mitochondrial fission and reduces I/R injury in diabetic mouse hearts.

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备注/Memo

备注/Memo:
收稿日期:2017-08-30.基金项目:国家自然科学基金项目资助(81670354,81600235) 通讯作者:丁铭格,主治医师,博士,主要从事糖尿病心肌病研究 Email:435411499@qq.com 共同通讯作者:付锋,讲师,博士,主要从事心肌保护研究 Email:fufeng048@126.com 作者简介:刘铮,本科生 Email:865663872@qq.com
更新日期/Last Update: 1900-01-01