Effect Of Telmisartan On The Expression Of Connexin-43 And TNF-α In Rats With Acute Myocardial Infarction

Background and ObjectivesAlong with the social economic development and the change of people's life style, the incidence of cardiovascular diseases has been increased year by year. Myocardial infarction belongs to a serious type of coronary heart disease.Among these, acute myocardial infarction has the highest mortality which seriously threatens people's life. As we know, arrhythmia always exists in the early stage of acute myocardial infarction. Ventricular arrhythmia is always the fatal arrhythmia, but its mechanism is still no very clear.so it is of great importance for us to study the mechanism.Rent studies show that abnormal expression and distribution of gap junction connexin can lead to the abnormal structure and function of gap junction,which has a close correlation with the occurence and continuity of arrhythmia. The abnormal distribution of gap junction connexin will cause the ventricular arrhythmia after myocardial infarction. The rearch result indicates that the increase of angiotensinⅡmay lead to the decreased expression of Cx43,but angiotensin type 2 receptors antagonist can upregulate the expression of Cx43 in rats with myocardial infarction and improve the connexin43 remodeling in rat after myocardial infarction. The reason why this happens is still not clear. It is found that the over-expression of tumor necrosis factor-a can bring about ventricular arrhythmia and electrical remodeling in myocardial cells of rat. It is also found that TNF-αcan inhibit the expression of Cx43 gene through activating JNK signal system, which restrain the functions of gap junction intercellular communication (GJIC)with the in-depth study by scholars, it is deemed that the drugs exert effect on the structure and distribution of gap junction connexin. Such viewpoint provides a new area to the therapy of arrhythmia. Telmisartan is an angiotensin-Ⅱreceptor antagonist. It can improve vascular endothelial function, reverse the atherosclerosis and ameliorate the Myocardial remodeling and cardiac function. There is still not studies at home and abroad on the effects of angiotensin-Ⅱreceptor antagonist on the Cx43 remodeling and the expression of TNF-a after myocardial infarctionIn our study, the rats model with myocardial infarction were choosed as the reseaech object. The expression of TNF-a and gap junction connexin 43 in rats with myocardial infarction was observed by immunohistochemistry so as to analyze the interaction between the two indexes.In addition,the effect of telmisartan on TNF-a and gap junction connexin 43 in rats with acute myocardial infarction was also observed by Immunohistochemistry.We preliminarily explore the possible mechanism how telmisartan prevent and cure arrhythmia when the acute myocardial infarction happens, which will provide the theoretical basis for the prevention and treatment of ARB on fatal arrhythmia.Materials and Methods1.Experimental animals and grouping Experimental rats were provided by animal laboratory center of zhengzhou university. The qualification number was 410116.Rats were randomly divided into the sham-operation group, model group and telmisartan group.2. Model preparation and Detected index The rats were anesthetized by injecting Chloral hydrate into abdomen. The model of rats with acute myocardial infarction in the three groups was induced by ligating the left coronary artery. The HE staining were performed to observe the morphological changes of myocardial cells.The expressions of Cx43 and TNF-a in the the area of acute myocardial infarction, Non-ischemic area and the fringe of infarction were observed by Immunocytoch-emistry. we make use of the micro camera system to analyze the images of Immun-ocytochemistry3. Statistical Methods The statistical software SSPS16.0 for windows was exploited to analyse data. All the data were expressed by (x±s) deviation and difference were compared using the one way ANOVA and LSD test between each group in every time point. The significant difference was judged by P<0.05.Results1.The change of myocardial morphology The myocardial cells in the infacted arae of the model group had a large area of necrosis compared with sham group. This area of necrosis was replaced by extensive proliferation of fiber collagen tissue.The myocardial cells in non-nicrosis area arranged disorganized and had compensatory hypertrophy,with the inflammatory cells infiltrating. The volume of myocardial cells and the extent of thincking of myocardial fiber in intervented group was slighter than that in model group. The proliferation of fiber collagen tissue and the infiltration of inflammatory cells in intervented group was much lighter than that in model group.2. Cx43 expression Cx43 arranged disorderly compared with model group.The average value of optical density,the area of positive expression and integral optical density in sham group were all decreased significantly compared with model group, which demonstrate that the expression of Cx43 is damaged to some extent. The average value of optical density and integral optical density in telmisartan group were significantly higher than that in the model group.3. The expression of TNF-a The expression of TNF-a in sham group were sigficantly higher in model group (P<0.05).The average value of optical density and integral optical density of TNF-a in telmisartan group were less than that in model group,which demonstrates that the interference of drugs could, to some extent, alleviate the expression of TNF-a. The Cx43 in the infacted myocardium was negatively correlated with the expression of TNF-a.(r=-0.922)Conclusions 1.Cx43 degradates greatly and distributes disorderly when the acute myocardial infarction happens.It shows a high degree of heterogeneity and has a negative correlation with TNF-αexpression.2.Telmisartan can promote the expression of Cx43 and inhibit the expression of TNF-a in the infarcted myocardium of rats, which can protect myocardium and alleviate ischemic necrosis of the myocardium.