Effects Of Mitochondrial Calcium Uniporter On Diazoxide Against Ischemic Reperfusion Injury

Objective To investigate whether diazoxide induced cerebral preconditioning against brain ischemia-reperfusion via mitochondrial calcium uniporter. Methods The ischemia-reperfusion models were performed by thread occlusion of middle cerebral artery for2h,and then24h reperfusion.80rats were randomly divided into five groups:A group(sham-operated group), B group(ischemia-reperfusion group), C group(diazoxide group), D group(diazoxide-spermine group),E group(spermine group).After24h reperfusion,neuropsychological score, the infarct size, the percentage of apoptosis and the expression of cytochrome c and Bax in the ischemic cerebra were measured in above groups respectively.Besides,the mitochondrial calcium content([Ca2+]m),the activity of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px),the content of malondialdehyde(MDA) and nitric oxide(NO) of ischemic cerebra were observed.Results Compared with B group,diazoxide induced preconditioning in C group improved neuropsychological score,decreased the infarct size,decreased the percentagc of TUNEL-positive cells,attenuated the expression of cytochrome c and Bax, and attenuated [Ca2+]m, improved the activity of SOD and GSH-Px, decreased the content of MDA and NO, the differences above had statistic mean,P<0.05.However, the coadministration with spermine reversed the benefit of diazoxide,which attenuated the neuropsychological score, increased the the percentage of TUNEL-positive cells and the expression of cytochrome c and Bax, and attenuated the activity of SOD and GSH-Px, increased [Ca2+]m and the content of MDA and NO, the differences above had statistic mean,P<0.05. Conclusions The protective effect of diazoxide against brain ischemia-reperfusion by inhibiting mitochondrial apoptotic pathway and attenuating [Ca2+]m and peroxidation injury in rats may involve in the suppression of MCU during reperfusion.