Effect of Grape Seed Proanthocyanidin Extract on Renin-angiotensin System and AQP2 Protein Expression in Rats with Myocardial Infarction
Objective:To study the effect of grape seed proanthocyanidin extract(GSPE)on the renin-angiotensin system and aquaporin-2(AQP2)protein expression in myocardial infarction(MI)rats.Methods:Fifty-five specific pathogen free(SPF)Sprague-Dawley rats were randomly divided into healthy group,model group,simvastatin group,low-dose GSPE group,and high-dose GSPE group,with 11 rats in each group.Except for the healthy group,the other rats were prepared by coronary artery ligation to establish the MI model.After successful modeling.the rats in low-and high-dose GSPE groups were orally administered with GSPE solution at doses of 100 mg/kg and 400 mg/kg,respectively.The rats in simvastatin group were orally administered with 40 mg simvastatin solution.Hematoxylin-eosin(HE)staining was used to observe the morphology of myocardial tissue.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay was used to detect myocardial cell apoptosis.Echocardiography was used to monitor cardiac function.Radioimmunoassay was used to detect angiotensin Ⅱ(Ang Ⅱ),plasma renin activity(PRA),and aldosterone levels.Immunoblotting was used to detect the protein levels of AQP2,B-cell lymphoma/leukemia-2(Bcl-2),and Caspase-3 in myocardial tissue.Results:Compared with the healthy group,the left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)of rats in model group increased,while the ejection fraction(LVEF)and fractional shortening(LVFS)decreased(P<0.05).Compared with model group,LVEDD and LVESD in low-and high-dose GSPE groups and simvastatin group decreased,while LVEF and LVFS increased(P<0.05).There were differences between low-and high-dose GSPE groups,but no significant difference between high-dose GSPE group and simvastatin group(P>0.05).Compared with healthy group,the levels of Ang Ⅱ,PRA,and aldosterone in model group increased(P<0.05).Compared with model group,the levels of Ang Ⅱ,PRA,and aldosterone in low-and high-dose GSPE groups and simvastatin group decreased(P<0.05).The apoptosis rates of myocardial cells in healthy group,model group,low-dose GSPE group,high-dose GSPE group,and simvastatin group were(5.11±0.33)%,(46.22±3.97)%,(28.46±3.77)%,(15.42±2.33)%,and(16.34±2.57)%,respectively,with statistically significant differences between the groups(P<0.05).Compared with healthy group,the levels of AQP2 and Caspase-3 proteins in myocardial tissue of rats in model group increased,while the level of Bcl-2 protein decreased(P<0.05).Compared with model group,the levels of AQP2 and Caspase-3 proteins in myocardial tissue of rats in low-dose GSPE group,high-dose GSPE group,and simvastatin group decreased,while the level of Bcl-2 protein increased(P<0.05).Conclusion:GSPE shows a protective effect on MI,which can improve cardiac function,reduce myocardial cell apoptosis,and its mechanism may be related to the regulation of AQP2 protein expression.
myocardial infarctiongrape seed proanthocyanidin extractaquaporin-2,AQP2renin-angiotensin systemratsexperimental study