Protective Effects Of Diazoxide On Focal Cerebral Ischemia Reperfusion Induced Injury Rats And Its Mechanism

Objective: To investigate the potential protective effects of diazoxide on cerebralischemia-reperfusion (I/R) tissue mitochondrial ATP enzyme activity and brain tissue MDAcontent, SOD activity in rats , and further analyze the possible mechanism of Cerebral protectionof mitochondrial k-atp channels opener Diazoxide .Methods: thirty-six healthy male Wistar male rats were randomly divided into three groups:sham operation group (N group), cerebral ischemia-reperfusion group(I/R group), Diazoxidetreated group (DZ group ), each group of 12 rats. N group was the sham operation group; I/Rgroup was the ischemia-reperfusion group and received equivalence normal salineintraperitoneal injection in preoperative 30min ; DZ group received 5 mg/kg Diazoxideintraperitoneal injection in preoperative 30min.The models of the focal cerebralischemia-reperfusion rats were made by the middle cerebral artery occlusion (MCAO) usingwire in rats'brain. After ischemia for 1h and reperfusion for 24h, neurological function deficitmarking was scored by using the Longa scoring system. Postoperation 24h , the rats were put todeath by head cutting and taken out the brain. cerebral mitochondria Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase were measured by biochemical determination method andmalondialdehyde(MDA) content and superoxide dismutase (SOD)activity in the cerebral tissueswere measured by spectrophotometry. The pathological feature change of cerebral tissue wasdetected by HE staining around infarcts and Caspase-3 expression in rat cerebral infarct areawere detected by immunohistochemistry method . Data using SPSS13.0 for statistical analysis, P< 0.05 was regared as the difference was statistically significant.Result:1,Comparisoning with the I/R group, DZ group (5mg/kg) significantly improved theactivity of mitochondria Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase, enhanced the activity of SOD andsignificantly reduce MDA content in brain tissue, (P<0.05).2,diazoxide treat group (DZ group) brain ischemia reperfusion of pathology changesignificantly lighter than ischemia reperfusion group (I/R group);but DZ group compared with Ngroup have still different degrees of pathology change in brain ischemia reperfusion injury,group. 3,Compared with N group, I/R group expressions of caspase-3 enhanced atreperfusion in ischemic region (P<0.05). Compared with I/R group, DZ group significantlyreduced the expression of caspase- 3 (P<0.05) .ConclusiConclusion:Mitochondrial k-atp channels opener Diazoxide has potential neuroprotective effectagainst cerebral ischemia-reperfusion injury in rats. The protective neural function specificmechanisms may and the following aspects about:1,Improving brain tissue mitochondria the activity of Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase;Maintaining sodium pumps and calcium pumps stability and the mitochondria ions balancedistribution; Reduceing the mitochondrial membrane potentia and the mitochondrial oedema.2,Enhance the activity of SOD and the ability of scanvenge oxygen free radicals; Reducethe MDA generation and inhibit lipid peroxidation , decrease oxygen free radicals on the neuronsdamage.3,Reduce the expression of caspase-3 in brain ischemia-reperfusion region , prevent cellapoptosis.