Relationship Between Changes Of AngⅡ And TGF-β/Smads And Ventricular Remodeling In Myocardial Tissue Of SHR And The Effect Of Enalapril Intervention

Objective:To elucidate the mechanism of enalapril in improving ventricular remodeling,and the relationship between AngII and TGF-β/Smads in myocardial tissue.In this study,SHR were selected as the study subjects,and a rat model of ventricular remodeling was constructed.Enalapril was used for antihypertensive therapy and explore the potential mechanism of enalapril to improve ventricular remodeling.Methods:（1）12 male,14-week-old,SHR and 12 male,age-matched,WKY were selected as subjects to measure their body weight,blood pressure（BP）,heart ultrasound.And heart histopathological changes were explored to explore the developmental time of ventricular hypertrophy in SHR.（2）24 male,14-week-old,SHR were randomly divided into a model group and an enalapril group（n=12）.The same age of WKY was used as a control group.And the body weight and BP were measured weekly.The enalapril group was administered by intragastric administration at a dose of 1.05 mg/（Kg.d）^-1for 14 weeks.The model group and the control group were given the same amount of distilled water.Rats underwent echocardiography to assess changes in cardiac conformation and cardiac function.After that all the rats were harvested.Serum and myocardial tissues were taken,and serum BNP,ST2,AngII and rat myocardial AngII levels were measured by ELISA.Cardiac specimens were taken and HE staining and Masson staining was performed to evaluate the morphological changes and myocardial fibrosis of rat.RT-PCR was used to detect the mRNA expression of TGF-β,CCN2,Collagen 1a,Collagen 3a,α-SMA,β-MHC and BNP in rat myocardium.The expression levels of TGF-β,Smad2,Smad3,Smad7,p-Smad2/3 and CCN2 in rat myocardium were detected by Western Blot.Results:1.1)SHR BP was significantly higher than that of WKY.Echocardiography and cardiac histopathological examination showed that the ventricular remodeling of ventricular hypertrophy and myocardial fibrosis was observed in 28-week-old SHR.1.2)The serum BNP and ST2 of SHR were higher than the same age of WKY（P<0.05）,and the BNP and ST2 of SHR in 28 weeks were significantly increased compared with the 24th week.2.1)BP monitoring showed that the BP of the model group was significantly higher than that of the control group（P<0.05）,and the BP of the enalapril group was lower than that of the model group（P<0.05）.2.2)The results of cardiac ultrasound showed that the septal thickness,left ventricular posterior wall thickness and left ventricular mass was increased in the model group（both P<0.05）,however,was decreased in the enalapril group（both P<0.05）.And the left ventricular diameter,left ventricular volume,ejection fraction and short axis shortening rate was obviously decreased,and increased in the enalapril group（both P<0.05）.2.3)The cardiac index of the model group was significantly increased（P<0.05）,and decreased in the enalapril group（P<0.05）.2.4)HE staining showed that the myocardial cells in the model group were hypertrophied and disordered,and smaller in the enalapril group.Masson staining showed that the myocardial fibers in the model group were heavier and the collagen volume fraction increased（P<0.05）and decreased in the enalapril group（P<0.05）.2.5)Serum BNP,ST2,AngII and myocardial AngII levels were significantly increased in the model group（P<0.05）and decreased in the enalapril group（P<0.05）.2.6)The results of RT-PCR showed that the expression of TGF-β,CCN2,Collagen 1a,Collagen 3a,α-SMA,β-MHC and BNP were increased in the model group（P<0.05）and decreased in the enalapril group（P<0.05）.2.7)The expression of TGF-β,Smad2,Smad3,p-Smad2/3 and CCN2 in the model group was increased and decreased in the enalapril group（P<0.05）;the Smad7 was increased in model group and decreased in enalapril group.Conclusion:1)The 28-week-old SHR can successfully construct a cardiac hypertrophy animal model.2)AngII in SHR myocardial tissue and circulation is at a high level,which promotes TGF-β/Smads related protein signal transduction in myocardial tissue,promoting myocardial fibrosis.3)Enalapril can reduce SHR blood pressure,myocardial fibrosis and reduce ventricular remodeling by reducing the level of AngII in tissues and circulation,and can down-regulating the transmission of TGF-β/Smads signaling in myocardial tissues.