| ObjectiveDiabetic cardiomyopathy is a specific cardiomyopathy that occurs in the absence ofcoronary artery disease and systemic hypertension. Oxidative stress induced byhyperglycaemia may be the main cause and the further activation of matrixmetalloproteinase-9(MMP-9) through oxidative stress can lead to cardiacremodeling,hypertrophy and mycardial fibrosis which ultimately result in chronic heartfailure.Exendin-4is the analog of glucagon-like peptide1(GLP-1) which is a new drug of type2diabetes. Studies show that GLP-1can regulate insulin secretion and￡-Cellproliferation,attenuate insulin resistance and reduce meal size, while hypoglycaemia israre. GLP-1recepter have been found not only in pancreace but in heart,vascular vesselgastrointestinal tract and kidney.Therefore,its effects except lowering blood glucose areworth studing.The present study aims to explore the expression of cardiac HO-1andMMP-9to examine whether hyperglycaemia-induced cardiac damage can be altered byexendin-4administration and its mechanism.Methods1Type2diabetes model was established in24wistar rats by high energy diet and lowdose of STZ.As a normal contol group,6normal rats were involved.2The rats with type2diabetes were randomly divided into3groups,2groups treatedwith high or low dose of exendin-4for6week respectively, and the other group was nottreated. Rats in normal control group were only given normal diet.3After6weeks of exendin-4administration, the blood glucose, plasma lipid ofmyocardium were observed and the expression of HO-1and MMP-9were detectedrespectively by biochemical methods and immunohistochemistry. HE staining was usedto show morphological changes of myocardium.4Statistical analysis: All values were treated with SPSS13.0, measurement date areexpressed as means±SD. The blood glucose, plasma lipid and the expression of HO-1andMMP-9were compared among groups using one-way analysis of variance. Differencebetween means of any two groups for date was assessed by t-test. Values of P<0.05were considered significant.Results1In DM versus NC group,BS lipid were higher. Compared those in the diabetic groupwith the Exendin-4injection group èBS lipid lowered in the exendin-4group and therewere significant difference between them.(P<0.05).The high-dose exendin-4group showa more clearer chang.(P<0.05).2In DM versus NC group, the expression of MMP-9were more obviouslyupregulated.The expression of HO-1was more significantly decreased ê Exendin-4treatment can significantly prevent these changes in diabetic rats. Compared between thetwo differenced-dose exendin-4injection group,the high-dose group expressed a morebeneficial effect.HE staining also showed the effect consistant with the change of BS lipid and MMP-9.Conclusion:1Diabetic cardiomyopathy in the rats can be ameliorated by exendin-4.2The protection of exendin-4on myocardium in diabetic cardiomyopathy isdose-dependent. |
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