Effect of Shenmai Injection on Improving Ventricular Remodeling in Rats with Chronic Heart Failure by Regulating TGF-β/Smads Signaling Pathway
OBJECTIVE:To probe into the mechanism of Shenmai injection(SMI)on improving ventricular remodeling in rats with chronic heart failure(CHF).METHODS:According to random number table method,40 rats were divided into sham surgery group(0.9%sodium chloride injection,intramuscular injection),model group(0.9%sodium chloride injection,intramuscular injection),positive control group(valsartan 10 mg/kg,intramuscular injection)and SMI group(Shenmai injection 0.38 mL/kg,intramuscular injection),with 10 rats in each group.Except for sham surgery group,another groups were established CHF model by ligation of left anterior descending coronary artery.After establishment of the model,the related drugs were administered once a day for 28 d.Echocardiography was applied to observe the changes of left ventricular and evaluate situation of cardiac function based on hemodynamics.Enzyme-linked immunosorbent assay(ELISA)were performed to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP),transforming growth factor-β1(TGF-β1),matrix metalloproteinases 9(MMP-9)and connective tissue growth factor(CTGF).Morphological changes of myocardium were observed by hematoxylin-eosin(HE)staining and MASSON staining.Expression levels of TGF-β1,Smad2,Smad3 and Smad7 were detected through quantification reverse transcription polymerase chain reaction.RESULTS:Compared with the sham group,the left ventricular ejection fraction(LVEF),left ventricular short-axis shortening rate(LVFS),left ventricular posterior wall thickness(LVPWs),aortic flow peak velocity(AV Peak Velocity),left ventricular pressure(LVP),left ventricular systolic pressure(LVSP),+dp/dtmax and-dp/dtmin in the model group decreased significantly;and left ventricular volume(LV vols),left ventricular end-systolic diameter(LVIDs),left ventricular end diastolic pressure(LVEDP)increased significantly;the serum levels of NT-proBNP,TGF-β1,MMP-9 and CTGF decreased significantly;the mRNA expression of TGF-β1,Smad2,and Smad3 increased significantly,the mRNA expression of Smad7 decreased significantly,with statistically significant differences(P<0.01).The morphological analysis showed that there was little cardiomyocyte remained in myocardium with structural disorder and serious degree of fibrosis.Compared with the model group,SMI can significantly increase the levels of LVEF,LVFS and LVPWs in the heart of rats with CHF,reduce LV vols and LVIDs,improve hemodynamics,and reduce the levels of NT-proBNP,TGF-β1,MMP-9 and CTGF,down-regulate the mRNA expression of TGF-β1,Smad2 and Smad3 and up-regulate the mRNA expression of Smad7,with statistically significant differences(P<0.01).SMI can inhibit myocardial cell necrosis and alleviate myocardial fibrosis.CONCLUSIONS:SMI could inhibit ventricular remodeling and achieve anti-CHF effects by participating into enhancing cardiac function,improving hemodynamics,alleviating myocardial injury,reducing the degree of fibrosis and regulating TGF-β/Smads signaling pathway.
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