| Background and objectivesAcute myocardial infarction (AMI) is a leading cause of death worldwide and remains one of the major killers in modern soceity. Progressive enlargement of the heart chamber and deterioration of contractile function after AMI, termed post-MI ventricular remodeling, is associated with development of heart failure and poor prognosis..Modification of neurohormonal acitivities mechanism, particularly the activation of rennin-angiotensin-aldosterone system (RAAS),can significantly influence the process of ventricular remodeling after AMI. The angiotensinⅡ, the primary active molecule of RAS, is thought to be produced by local synthesis rather than from circulating angiotensinI.Ang Ⅱ can induce the increases in cardiomyocyte size,interstitial fibrosis,and contractile dysfunction. Fibrosis and myocyte hypertrophy are classical remodeling parameters in heart failure,which is highly associated with cytoskeleton rearrangement.The cytoskeleton is an active framework of cytosolic filaments composed of3types of protein fibers,the microtubules,the intermediate filaments,and the microfilaments.Microfilaments made up essentially of actins,actin binding proteins and myosins are the thinnest and most flexible filaments.Hsp27(Heat shock protein27),a chaperone protein,is known to bind actin in vitro,and this observation led to the study that Hsp27regulates actin filament dynamics. Treatment with valsartan,an angiotensin receptor blocker(ARB), resulted in changes in cardiac volume and ejection fraction and improved survival and reducing cardiovascular mortality in patients who suffered an MI. However,how Ang II regulated the rearrangement of cytoskeleton and led to the heart failure are not fully illuminated.Therefore,we focus on the possible molecular mechanisms of AngⅡ to modulate the actin cytoskeleton rearrangement which led to the heart failure,and the reverse effects of valsartan. This thesis is intended to provide a theoretical basis for the positive effects of valsartan on the prevention and cure of ventricular remodelling when the acute myocardial infarction happens.Methods1.60pcs healthy and male mature Sprague-Wistar rats with the weight225-275g/pc and the age8weeks old respectively,were randomly assigned to four groups:normal control group(group N, n=15), sham-operation group(group SH,n=15), the acute myocardial infarction model group(group AMI, n=15) and valsartan treatment after the acute myocardial infarction group(group X, n=15).2.Injected10%Chloral hydrate into abdomen to anesthetize the rats which had been weighed. Under the condition of respirator, ligated the left coronary artery to induce the acute myocardial infarction model of rats.Rats in group X were administered with valsartan (15mg/kg/d) using gastric gavage for weeks,which were completed at the same time everyday.The other three groups in the same manners were given the same amount of physiological saline.3.After hematoxylin-eosin(HE) staining,samples through the olympus optical microscope were carefully observed on the morphological changes of these myocardial cells.4.The expression of F-actin and HSP27protein and mRNA were detected by immunohistochemistry and RT-PCR respectively.The relative expression F-actin and HSP27protein and mRNA in the four groups were used in SPSS drawing function to establish the scatter diagram, and then analysed by pearson correlation. 5.Analyse the data by exploiting the statistical software SSPS17.0for windows.All the quantitative data were presented as means±standard error(x±s). Multiple comparisons were completed by using the one way analysis of variance (ANOVA,and the sattistical significance of differences between the two groups was assessed with the least-significant difference(LSD) test;correlation analysis used pearson correlation analysis. Sattistical significance was set at α<0.05.Results1.The morphological changes of myocardial tissues The myocardial cell in group SH and in X ranged in order,with no fibers fractured, the normal myocytes in MI group and in X group was disappeared or distributed disorderly.The proliferated collagen fiber were taken the place of the necrotic myocytes,and the abruption and disorganized of myocardial fibers in residual myocardium were also observed.Compared with group MI,the number of the necrotic myocytes and the proliferation of collagen fiber in group X were smaller and less respectively.2.The amout of HSP27and F-actin protein and mRNA detected by immunohistochemistry and RT-PCR in group X and group AMI were higher than those in group SH (P<0.05),and it was higher in group AMI than that in group X (P<0.05).It had no difference in group N and group SH (P>0.05). The expression of cytoskeletal protein of F-actin and HSP27in group AMI and group X was a positive correlation (P<0.05),and there was no correlaton between the expression of protein and mRNA of F-actin and HSP27in group N and group SH (P>0.05)conclusions1.In the infarct and border zone,the expression of HSP27and F-actin protein and mRNA increased significantly after acute myocardial infarction.They seemed to be positive correlation.2.Valsartan can reduce the the expression of HSP27and F-actin protein and mRNA in the infarct and border zone. Valsartan can relieve the ventricular remodelling and alleviate cardiac function. The molecular mechanisms of alleviate ventricular remodelling maybe through blocking angiotensin Ⅱ adverse impact, and then inhibited the rearrangement of cytoskeleton. |
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