| Background:myocardial infarction ventricular remodeling after MI is the process of variety of neuroendocrine regulation system and intracellular signal transduction mechanism activated, causing myocardial cells, non-myocardial cells, extracellular matrix matter changes, structural and functional changes. Mainly for the infarct zone wall thinning, myocardial necrosis, fibrosis; non-infarction zone myocardial cells compensatory hypertrophy, cardiac myocardial apoptosis, extracellular matrix changes, and further can cause right ventricular remodeling, eventually leading to heart morphology dysfunction, heart failure. After myocardial infarction, RAAS is activated, the extra cellula rmatrix increased, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) balance is broken.TGF-β1is a fibrosis factor, increased expression in myocardial fibrosis, which is the target for anti-fibrotic therapy. Activated TGF-β1/Smads signal pathway in myocardial injury and repair, regulate inflammation and fibrosis reaction involved in the structural process of ventricular remodeling. Notch signaling pathway was found in Drosophila firstly, which was widespread in invertebrates and vertebrates, and are highly conserved, the function through local cell interactions, involved in cell differentiation and apoptosis. The over-expression or deficiency of Notch signaling protein can cause cardiac abnormalities. Studies have shown that Notch signaling plays an important role in remodeling, which reduced expression in TGF-beta induced cardiac fibroblasts to myofibroblasts. Then in the process of ventricular remodeling, the expression of Notch signal, and TGF-beta1whether there is contact, further research is needed.Objective:Based onanimal models of myocardial infarction, blood theory as a guide, using the early experimental the most significant effect Yiqihuoxue2:1group to intervene, the use of echocardiography testing,immunohistochemical(IHC) techniques investigate the formation of myocardial infarction ventricular remodeling and Yiqihuoxue drug’s effect from cardiac structure, function, and microvascular. From the perspective of molecular biology to explore TGF-beta, Notch-related gene and protein expression in the remodeling and Yiqihuoxue drug of its role. To use bioinformatics analysis of the effect of Yiqihuoxue drug, further reveal the molecular mechanisms of Yiqihuoxue drug.Methods:1Build an animal model of acute myocardial infarction by left coronary artery ligation surgery and randomly divided into MI group, Yiqihuoxue group, Tongxinluo group, perindopril group, together with the sham-operated group. Second postoperative day administrated the rats in each group, respectively after7days,28days get specimens.2Using echocardiogram test for7th day,28th day each time point cardiac function, immunohistochemical test micro-vascular expression, HE pathological staining, Masson staining observe infarct zone and non-infarct zone structure, collagen expression. Using real-time quantitative PCR(Q-PCR) and Western blotting(WB) test MMP2gene and protein expression, comprehensive evaluate the formation of myocardial infarction ventricular remodeling and Yiqihuoxue drug’s influence.3Using real-time quantitative PCR(Q-PCR) to detectrat heart tissueTGF-β1, Notch1, Notch2, Notcb3, Notch4, RBPJ, Hes-1gene expression at the7th day,28th day time point. Detect TGFβ1, Notchl, Notch3, Notch4, Hes-1protein expression by Western Blotting. Explore the TGF-β1and Notch signaling in the post-infarction ventricular remodeling in rat myocardial tissue expression and Yiqihuoxue drug influence. Through the correlation analysis reveals the relationship between TGF-β1and Hes-1protein.Results:1Echocardiography comparison of test results:MI group’s rats left ventricular diastolic dimension(LVDd), left ventricular systolic dimension (LVDs) compared with the sham group increased at the7th day,28th day time point,the difference was significantly(P<0.05), after the administration’s invention, administration group LVDs compared with the MI group was significantly lower(P<0.05); MI group left ventricular fractional shortening (FS),left ventricular ejection fraction(EF) compared with the sham group decreased; Masson staining show that at each time point MI group collagen expression compared with the sham group was significantly increased, after the administration the collagen expression decreased; Micro-vessel count (MVC) results show that the number of MI group at each time point micro-vascular compared with the sham group increase(P<0.05),after the intervention comparedwith the model group, the MVC increased expression and the28th day more significantly(P<0.05). MMP2gene and protein results show that at each time point MI group were compared with the sham group increased(P<0.05), after intervention the gene expression decreased and the7th day obviously(P<0.05).2Real-time PCR results showed that the MI group’s TGF-β1of Notch1, Notch3, and Hes-1gene expression compared with sham-operated group increased, after intervention the expression on a downward trend, in which of Notchl, Notch3, Hes-1gene significantly (P <0.05). After the intervention, the differences of TGF-β1gene and protein expression in the7th day and28th day were significantly (P<0.05). Notch1, Hes-1protein expression in the7th day and28th day have decreased, but the expression of Notch1protein7th time point was significantly lower (P<0.05), Hes-1protein expression in the28th day the difference was significantly (P<0.05); Based on the correlation analysis TGF-β1and Hes-1proteinin rat myocardium after myocardial infarction were significantly correlated (R2=0.968,P<0.05).Conclusion:1Yiqihuoxue drug has better regulation on the structure, function, extracellular matrix of rat heart, which improve ventricular remodeling from improve heart function, reduce myocardialcell hypertrophy, promote neovascularization.2Yiqihuoxue drug has anti-fibrosis effect by inhibiting TGF-betal, thereby increasing EF, improve ventricular remodeling through the inhibition of Notchl, of Notch3, Hes-1on myocardial cell differentiation impact,and the relationship is correlation between Notch signal and TGF-beta signal. |
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