| Objective: To observe the effects of Aconitou Chishizhi pills(ACP)on cardiac hypertrophy index,pathological changes of cardiac tissue,oxidative stress and apoptosis signaling pathway protein expression in cardiac tissue of rats with cardiac hypertrophy after acute myocardial infarction.To investigate the protective effect and mechanism of ACP on cardiac hypertrophy after acute cardiac infarction in rats,so as to provide experimental basis for clinical application.Methods: Forty SD male rats were randomly divided into normal group,model group,western medicine control group and Aconitou Chiishizhi pill group,with 10 rats in each group.Preparation of cardiac hypertrophy(CH)model after acute myocardial infarction(AMI):Except for the normal group,the rats in the other three groups were anesthetized,and AMI model was established by ligating the left anterior descending coronary artery and then feeding for 28 days to establish the Cardiac hypertrophy model after acute myocardial infarction.The rats in the normal group and the model group were given saline 6.67ml/(kg·d)by gavage,the rats in the western medicine control group were given perindopril0.4mg/(kg·d)by gavage,and the rats in the ACP group were given ACP solution 4.9g/(kg·d)by gavage.The drug was administered continuously for 28 days.The electrocardiogram(ECG)of the rat AMI model was observed.Cardiac hypertrophy index;HE staining was used to observe the pathological changes of myocardial tissue.Masson staining was used to observe myocardial fibrosis in each group.The serum levels of ANP,Ang II,ALD and HYP were determined by ELISA.The levels of SOD,MDA and ROS in myocardial tissue were measured by colorimetry.Immunohistochemistry was used to detect the expression of Keap1 and Bcl-2 proteins in myocardial tissue.WB was used to test the protein expression levels of Keap1,Nrf2,HO-1,NQO-1,Bcl-2,and Bax in myocardial tissue.Results:1.Effects of ACP on Cardiac hypertrophy index in rats after AMICompared with the normal group,the Cardiac hypertrophy index(HW/BW,LVW/BW)in the model group was increase remarkably(P<0.01);Compared with the model group,the Cardiac hypertrophy index(P<0.01),and the ACP group was lower than the western medicine control group.2.To investigate the effects of ACP on pathological changes of myocardial tissue in rats with CH after AMIThe margins of cardiomyocytes in the normal group were clear,the distribution was uniform,Nuclear ellipse centered,the muscle fibers were arranged regularly,and the texture was neat.In the model group,the gap between cardiomyocytes was widened,the cross-sectional area was increased,the myofibrils were thickened,the nucleus was branched,some nuclei disappeared,and most of the cells were swollen,with interstitial hyperplasia and inflammatory infiltration.Compared with the model group,the ACP group and the western medicine control group had regular structure of myocardial cells,lessen fibrosis,decrease cell swelling,thanatosis and seep inflammatory cells,especially in the ACP group.Image J analysis showed that the cross-sectional area(CAS)of cardiomyocytes in the model group was increase remarkably than that in the normal group(P<0.01).Compared with the model set,the CAS of the western medicine control group was decreased(P<0.05),the CAS value of the ACP group was significantly decreased(P<0.01).3.Effects of ACP on myocardial fibrosis in rats with CH after AMIThe myocardial cells of rats in normal group were closely arranged and regular,the muscle fibers were arranged in bundles,and there was no collagen fiber deposition.The myocardial cells in the model group were distorted and hypertrophic,the fibers were broken,the gap was widened,the arrangement was disordered,and the interstitial proliferation was serious.Compared with the model group,the ACP group and the western medicine control group had significantly reduced myocardial collagen fiber hyperplasia,collagen deposition,and pathological changes.It was obviously alleviated by ACP.4.Effects of ACP on serum ANP,Ang II,ALD and HYP in rats with CH after AMICompared with the normal group,the levels of ANP,Ang II,ALD and HYP in the serum of the model group were increase remarkably(P<0.01);Compared with the model set,the contents of ANP,Ang II,ALD and HYP in the serum of the ACP group and the western medicine control group were decreased,and the contents of Ang II and ALD in the ACP group were decreased(P<0.05),and the contents of ANP and HYP were significantly decreased(P<0.01),ANP and Ang II in the western medicine control group decreased(P<0.05),and the contents of ALD and HYP were significantly decreased(P<0.01).5.To investigate the effects of ACP on SOD,MDA and ROS in myocardial tissue of rats with CH after AMICompared with the normal group,the SOD activity in myocardial tissue of the model group was increase remarkably(P<0.01),and the contents of MDA and ROS were prominent enhancement(P<0.01);Compared with the model group,the activity of SOD in the ACP group and the western medicine control group was significantly increased(P<0.01),and the contents of MDA and ROS were significantly decreased(P< 0.01).6.Effects of ACP on the expression of Keap1 and Bax proteins in myocardial tissue of rats with CH after AMIImmunohistochemical method showed that,Compared with the normal group,the expression of Keap1 was higher and Bcl-2 was lower in the myocardial tissue of the model group.Compared with the model group,the expression of Keap1 was significantly decreased and the expression of Bcl-2 was significantly increased in the Aconitou Chiishizhi pill group and the western medication control group.7.To investigate the effect of ACP on the expression of Keap1,Nrf2,HO-1,NQO-1,Bcl-2 and Bax proteins in myocardial tissue of rats with CH after AMIWestern blot analysis showed that,Compared with the normal group,the expression of Keap1 in the model group was prominent enhancement(P<0.01),decreased NQO-1expression(P<0.05),Nrf2 and HO-1 expressions were significantly decreased(P<0.01).Compared with the model group,the expression of Keap1 was significantly decreased(P<0.01),Nrf2,HO-1,and NQO-1 expression were significantly increased(P<0.01).Compared with the normal group,the expression of Bcl-2 in the model group was decreased(P<0.05),Bax expression was significantly enhancement(P<0.01).Compared with the model group,the expression of Bcl-2 in the ACP group was significantly increased(P<0.01),Bax expression was significantly decreased(P<0.01),while the expression of Bcl-2 in the western medicine control group was increased(P<0.05),Bax expression decreased(P<05).Conclusion: ACP can inhibit the development of CH and reduce the degree of myocardial fibrosis after acute myocardial infarction in rats,and its mechanism may be through regulating the RASS system,reducing the contents of ANP,Ang II,ALD and HYP in serum,and activating Keap1/Nrf2/HO-1/NQO-1 and apoptosis signaling pathways.It can reduce oxidative stress injury and myocardial cell apoptosis,and achieve the inhibitory effect on CH. |
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