Effect Of Enalapril On Expression Of ACE2and TGFβ1in Rats With Chronic Congestive Heart Failure

Objective Determination of enalapril on rat model of chronic heart failure (CHF) hemodynamic changes,and to detect rat cardiomyocytes angiotensin converting enzyme2(ACE2) and the protein expression of the transforming growth factor-β1(TGF-β1), the thesis elaborate protection mechanisms of of enalapril on chronic congestive heart failure (CHF) myocardial cells to provide a theoretical basis for the safety and efficacy of enalapril in the treatment of CHF.Methods Choose45weight from250to280g male SD rats, divide into the control group(CON),congestive heart failure(CHF)group, enalapril+CHF group (The following calls enalapril group). CHF group were injected with adriamycin (ADR)(concentration for1mg/ml, each rat was given2.2mg/kg), For Once a week,10consecutive weeks, Heart failure models,and then observed for2weeks; Control group was given the same dose of saline instead of adriamycin, method was same as above. Enalapril group were injected with enalapri(concentration for10mg/kg·d)after injecting with doxorubicin hydrochloride (concentration was same as CHF group) to intervene, and injected adriamycin once a week until the12th week. After12weeks, we measured heart function and blood flow dynamics indicators of each rat, and then killed all the rats, take the hearts and weighed left ventricular mass and quality of the heart of experimental rats and immunohistochemical detected protein expression of ACE2and TGF-β1by immunohistochemistry.Results Comparing with the control group, left ventricular wall becomes thinner, ventricular cavity expand of CHF group and enalapril group; CHF rats appeared bloody ascites, pleural effusion and liver congestion nodes; the symptoms of heart failure of enalapril group significantly reduced compared with CHF group.Heart function tests showed, compared with the control group, Left ventricular end diastolic diameter (LVEDd), Left ventricular systolic dimension (LVESd) of the CHF group and enalapril group were significantly increased (P<0.01), Left ventricular ejection fraction (LVEF) of CHF group and enalapril group was significantly lower (P<0.01) Compared with the CHF group, LVESd and LVEDd of enalapril group were significantly lower (P<0.01), LVEF was significantly increased (P<0.01)Hemodynamic analysis showed that, compared with the control group, the absolute value of pressure maximal rate of rise,(+dp/dt max) and pressure maximal rate of fall v-dp/dtmax) of the CHF group and enalapril group were significantly lower (P<0.01), Left ventricular end pressure (LVEDP) was significantly increased (P<0.01). Compared with the CHF group, absolute value of+dp/dtmax, and-dp/dtmax of enalapril group, LVSP were significantly increased (P<0.01), while LVEDP was significantly lower v(P<0.01). In addition, compared with the control, CHF and in accordance with that in Group Body weight was significantly lower (P<0.05, P<0.01); enalapril group rats quality compared with the CHF group tended to increase, but not statisticallysignificant (P>0.05). CHF group and in accordance with that in Group CHF rats LVMI compared with the control group was significantly higher (P<0.01); according to enalapril group LVMI was significantly lower than the CHF group (P<0.01)HE staining showed that, compared with the control group, cardiomyocyte hypertrophy, decrease in the number of myocardial cells, fibrosis, some myocardial necrosis flaky of CHF group and enalapril group; Compared with the CHF group, myocardial injury reduced, enalapril group is basically between the control group and the CHF group. Immunohisto-chemistry of TGF-β1and ACE2of myocardial cells showed that, compared with the control group, protein expression of of CHF group and enalapril group, TGF-β1was significantly increased (P<0.01). Compared with the enalapril group, protein expression of TGF-β1of CHF group was significantly increased (P<0.01) compared with the control group, ACE2protein expression of CHF group and enalapril group was significantly increased (P<0.01), compared with the enalapril group, ACE2protein positive expression of CHF group was significantly reduced (P<0.01)Conclusions1. Enalapril significantly improved morphological and hemodynamic parameters of heart failure rats doxorubicin-induced;2. Enalapril increaed ACE2protein expression and decreased TGF-β1protein expression of cardiomyocytes of heart failure rats doxorubicin-induced, which may be involved in improving the process of cardiac remodeling.