Background
Sevoflurane postconditioning (SevP) is an effective way in relieving myocardial ischemia/reperfusion (IR) injury, which doesn’t work well in diabetic myocardium unfortunately. Prior studies have noted the importance of increasing oxidative stress in diabetic tissues. Noteworthily, mitochondrial fission mediated by dynamin-related protein 1 (Drp1) is an upstream pathway of reactive oxygen production. Whether Drp1 dependent mitochondrial fission is associated with the ineffectiveness of SevP in diabetic myocardium remains unknown. The aim of this study was to explore the important role of Drp1 in diabetic myocardium and investigate whether Drp1 inhibition could restore the cardioprotective effect of SevP.
Methods
In the first part, adult male Sprague-Dawley(SD) rats were divided into 6 groups. Rats in diabetic groups were fed with high-fat and high-sugar for 8 weeks, and then received a injection of streptozotocin (35 mg/kg) intraperitoneally. Myocardial IR was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion༎SevP was applied by continuous inhalation of 2.5% sevoflurane 1 min before reperfusion, which lasted for 10 min. In the second part, mdivi-1 was used to investigate whether Drp1 inhibition could restore the cardioprotective effects of SevP in diabetic myocardium against I/R injury. The myocardial infarct size, pathology, mitochondrial ultrastructure, cardiomyocyte apoptosis, total SOD activity, MDA content, and Drp1 expression were detected.
Results
The diabetic myocardium displayed severer injury with greater infarct size and apoptosis. Up-regulated Drp1 expression concomitant with increased mitochondrial fission and oxidative stress were observed in diabetic myocardium subjected to I/R. The deteriorated changes were alleviated in normal but not in diabetic rats. Importantly, mdivi-1 administration significantly suppressed mitochondrial fission and oxidative stress, and the beneficial effects of SevP were restored by mdivi-1.
Conclusions
The present study indicates a crucial role of Drp1 dependent mitochondrial fission in diabetic myocardium subjected to IR. Drp1 inhibition may be effective in restoring the effect of SevP in reducing diabetic myocardial IR injury.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.