Effects of ghrelin on myocardial remodeling matrix metalloproteinases expression in post-myocardial infarction rats with diabetes mellitus

Abstract:

Objective：To investigate the effects of ghrelin on myocardial remodeling matrix metalloproteinases expression in post-my－ocardial infarction diabetic rats. Methods：Adult male SD rats were divided into four groups：myocardiac infarction（ＭＩ），diabetes mellitus+myocardiac infarction（DM+MI），DM+MI+ghrelin，DM+MI+ghrelin+GHSR1a inhibitor[D-Lys3]-GHRP-6. Diabetes was in－duced by injection of streptozotocin（STZ，60 mg/kg）. After three months，left anterior descending artery（LAD） ligation was performed in all groups. DM+MI+ghrelin group received ghrelin，200 ?滋g/（kg·d）. DM+MI+ghrelin+[D-Lys3]-GHRP-6 group received ghrelin， 200 ?滋g/（kg·d） and [D-Lys3]-GHRP-6，50 mg/（kg·d）. The other two groups received the same amount sterile normal saline only. Four weeks later，Sirius red staining was used to detect myocardial fibrosis. Myocardial infarct size was detected by Masson staining. The distribution and expressions of matrix metalloptoteinase-2（MMP-2），matrix metalloptoteinase-9（MMP-9） and tissue inhibitor of metalloprotroteinase-1（TIMP-1） were detected by immunohis－tochemistry and Western blot，separately. Results：Myocardial collagen volume fraction（P=0.003），myocardial infarct size（P=0.001），the expression of MMP-2（P=0.000） and MMP-9（P=0.000） were significantly increased in DM+MI group than in MI group. After ghrelin administration，myocardial collagen volume fraction（P=0.001），myocardial infarct size（P=0.005），the expres－sion of MMP-2（P=0.001） and MMP-9（P=0.001） were significantly decreased in diabetic rats complicated with MI. TIMP-1 was sig－nificantly higher in diabetic groups than in MI group（P=0.000），without significant difference among these groups（P ＞0.05）. However，[D-Lys3]-GHRP-6 blocked the above effects of ghrelin. Conclusion：Ghrelin can inhibit myocardial extracellular matrix remodeling and reduce myocardial infarct size by suppressing the expressions of MMP-2 and MMP-9.