| Objective To investigate the interventional effect of olmesartanmedoxomil on myocardial neovascularization and its possibly underlyingmechanism in ischemic myocardium of rats with myocardial infarction byobserving the effects of olmesartan medoxomil on myocardialmorphological changes,microvascular density(MVD),myocardial infarctarea and the expressions of Angiogenin-1(Angpt-1) in ischemicmyocardium of rats with Acute Myocardial Infarction(AMI).Methods Healthy adult male Sprague-Dawley(SD) rats wereselected and the acute myocardial infarction models was established byligating the left anterior descending branch of the coronary artery.Starting24h after ligation,surviving thrity male SD rats were randomly divided intothe AMI model group(the AMI group,n=15) and olmesartan medoxomilgroup(the OM group:3mg·Kg-1·d-1,n=15).The remaining15ratsundergoing thoracotomy but not coronary ligation served as sham opertion control group. Olmesartan medoxomil was administered through gavageone day at a time24hours after operation,the AMI group and Sham groupwere fed with physiological saline in the same volume and the samemethod. On7th、14thand28thdays after operation,5rats in each group weresacrificed and their hearts were harvested.Hematoxy-eosine(HE) stainingwere used to observe myocardial morphological changes and to measuremyocardial infarct areas.Masson staining were used to observe myocardialfibrosis changes. Immunohistochemical(IH) technique was applied tocalculate the number of microvascular density(MVD) and to evaluate theexpression of Angpt-1proteins in peri-infarction areas.RT-PCR techniquewas used to determine the levels of Angpt-1mRNA in ischemicmyocardium of heart tissue.All the treatments for animals were accordedwith the animal ethical standards.Results All45rats were included in the final analysis.Under lightmicroscope,heart tissue showed nomal HE dyeing features in GroupSham,the transverse strication were clear,cardiac muscle fiberwell-arranged,no inflammatory cell infiltration.Group AMI and Group OMobserved inflammatory cell infiltration,cardiomyocyte swelling,section ofmyocardium dissolved and even fibrosis in ischemic myocardium could beobserve,at non-infarction zones cardiac muscles arrangedregularly.Compared with AMI group,myocardial infarct area decreased inOM group,distinction were significantly different in statistics(P＜ 0.05).Group Sham not yet observed obviously expression of neogenesismicrangium. The expression of neogenesis micrangium positive staining bythe factor Ⅷ in peri-infarction area observed at7days after acutemyocardial infarction both Group AMI and Group OM,the vascular densityobviously increased at14days both of the two groups.MVD increased inGroup OM at the same time point compared with Group AMI(P＜0.05).Group Sham observed by change the scattered expression of Angpt-1at different time point.Different levels of expression of Angpt-1in GrourpAMI and Group OM at different time point, The expression of Angpt-1protein and mRNA was significantly higher in the OM group than that inthe AMI and Sham group at the same time point,the difference within thethree groups were significant (p＜0.05).Conclusion The increase of myocardial neovascularization afterAMI is associated with elevated expression of myocardialAngpt-1.Olmesartan medoxomil can enhance myocardialneovascularization and decrease the size of myocardial infarction.Thepossibly underlying mechanism may be that olmesartan medoxomil canincrease the expression of Angpt-1in AMI rats. |
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