Title: Effects of gliclazide on myocardial protection of isolated type 2 diabetic rat heart afforded by ischemic preconditioning
Abstract:The myocardial protection afforded by ischemic preconditioning(IPC) can alleviate ischemia-reperfusion injury in normal rat heart.However,this myocardial protection is seldom studied in the type 2 dia...The myocardial protection afforded by ischemic preconditioning(IPC) can alleviate ischemia-reperfusion injury in normal rat heart.However,this myocardial protection is seldom studied in the type 2 diabetic rat with myocardial ischemia disease.In this study,we aimed to evaluate the effects of ATP-sensitive potassium channels(KATP channels) on IPC in the isolated type 2 diabetic rat heart and the role of the sulfonylurea gliclazide.Methods Streptozotocin(STZ)-induced type 2 diabetic male Wistar rats with or without gliclazide(64 mg /kg body weight,orally) and age-matched non-diabetic control rats were used for all studies.The isolated hearts were perfused with Langendorff's system under the constant flow,pressure and temperature conditions with Kreb's-Henseleit solution(K-H).After 5 minutes of balance perfusion,these rats were randomly divided into six groups:non-diabetic control rats without IPC(CIR);non-diabetic control rats with IPC(CIP);diabetic rats without IPC(DIR);diabetic rats with IPC(DIP);gliclazide-treated diabetic rats without IPC(GIR);and gliclazide-treated diabetic rats with IPC(GIP).Groups CIR,DIR,and GIR were subjected to 30-min global ischemia and 60-min reperfusion for induction of ischemia /reperfusion injury.Groups CIP,DIP,and GIP were given three cycles of 5-min ischemia and 5-min reperfusion as IPC,and then ischemia /reperfusion injury program was implemented.Extent of ischemia /reperfusion injury was measured in terms of the release of lactate dehydrogenase(LDH),creatine kinase(CK),and creatin kinase-MB(CKMB) in coronary effluent.After perfusion,Kir6.2 and SUR2A mRNA expressions in the myocardial tissue were characterized by fluorescent quantitative real-time PCR method,and Kir6.2 and SUR2A protein expressions were assessed by immunohistochemistry.Result In non-diabetic control rats,the release of LDH,CK,and CK-MB in coronary effluent markedly decreased with IPC compared with No-IPC(P 0.05),but not in diabetic rats.However,in gliclazide-treated diabetic rats,IPC-induced decrease in the release of LDH,CK,and CK-MB was restored compared with No-IPC(P 0.05).The expressions of Kir6.2 both at mRNA and protein levels in CIP were significantly higher than those in CIR.There was no significant difference in the expression of Kir6.2 and SUR2A both at mRNA and protein levels between DIP and DIR.However,the expression of Kir6.2 both at mRNA and protein levels was significantly higher in GIP than in GIR.No significant difference was detected in the mRNA expression level of SUR2A between the six groups.The expression of SUR2A at protein level was significantly higher in CIP than in CIR and in GIP than in GIR.Conclusions The cardioprotective effect of IPC is abolished in the isolated type 2 diabetic rats compared with non-diabetic control rats.However,to some extent,gliclazide can improve the myocardial protection of IPC against ischemia /reperfusion injury,thus suggesting that it is mediated mainly by KATP channels at mRNA or protein level,which provides a basis for further investigating the effects of KATP channels on IPC.Read More
Publication Year: 2013
Publication Date: 2013-01-01
Language: en
Type: article
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