Changes in expression of mitochondrial fission protein dynamin-related protein-1 during myocardial ischemia-reperfusion injury in diabetic rats

Abstract

Objective To evaluate the changes in the expression of mitochondrial fission protein dynamin-related protein-1 (Drp1) during myocardial ischemia-reperfusion (I/R) injury in diabetic rats. Methods Sixty healthy adult male Sprague-Dawley rats, weighing 220-250 g, were randomly divided into 4 groups (n=15 each) using a random number table: sham operation group (group S), myocardial I/R group (group I/R), diabetes mellitus (DM) + sham operation group (group DS), and DM + myocardial I/R group (group DI/R). DM was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin in DS and DI/R groups.Myocardial I/R was produced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion in I/R and DI/R groups.At 120 min of reperfusion, the rats were sacrificed, and myocardial specimens were obtained for measurement of the myocardial infarct size.The myocardial specimens were cut into sections which were stained with haematoxylin and eosin to examine the pathological changes under light microscope.The ultrastructure of mitochondria in cardiomyocytes was observed by electron microscopy.Apoptosis in cardiomyocytes was determined by TUNEL.Apoptosis index (AI) was calculated.The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by the methods of xanthine oxidase and thiobarbituric acid, respectively.The expression of myocardial Drp1 protein and mRNA was determined by immunohistochemistry and real-time reverse transcriptase polymerase chain reaction, respectively. Results Compared with group S, the MDA content was significantly increased, the SOD activity was decreased, the expression of Drp1 protein and mRNA was up-regulated, and AI was increased in I/R, DS, and DI/R groups (P<0.05). Compared with group I/R, the MDA content was significantly increased, the SOD activity was decreased, the expression of Drp1 protein and mRNA was up-regulated, AI was increased, and the myocardial infarct size was enlarged in group DI/R (P<0.05). Compared with group DS, the MDA content was significantly increased, the SOD activity was decreased, the expression of Drp1 protein and mRNA was up-regulated, AI was increased, and the myocardial infarct size was enlarged in group DI/R (P<0.05). The pathological changes was aggravated in group DI/R compared with group I/R. Conclusion Myocardial I/R injury is aggravated in diabetic rats, and the mechanism may be associated with up-regulated expression of myocardial Drp1. Key words: Dynamins; Mitochondria; Myocardial reperfusion injury; Diabetes mellitus