| BackgroundAcute myocardial infarction (AMI) is an acute cardiovascular system disease, which is an extremely serious clinical type of coronary heart disease.The statistics show that the incidence of this disease has a steady annual increasing trend in recent years. Malignant arrhythmia after AMI is a most critically acute disease in cardiovascular system, especially simple and/or polymorphic ventricular tachycardia, ventricular fibrillation and some other rapid arrhythmia. They can exacerbate the existing cardiovascular disease, and they also may be the reason of induced cardiogenic shock and sudden death usually. The effect of conservative treatment of antiarrhythmic drugs is not very significant in the clinical work, the total efficiency of about 40% to 70%.The mechanism of arrhythmia in acute myocardial infarction is not entirely clear at present, therefore, a profound research of the mechanism of arrhythmia and to find new drugs target become the focus and the problem of antiarrhythmia.In recent years,people found that the abnormal electrical remodeling of the ion channels of myocardial cellular membrane in infarcted zone and myocardium of infarction surrounding after AMI plays a vital role in the development of acute ischemic heart arrhythmia,which may be the important mechanism of the formation and development of arrhythmia. The KCNE gene family encodes amino acid residues containing three structure domain:the N-terminal extracellular domain, the transmembrane region and the c-terminal cytoplasmic,which only include 1 transmembrane domain.They function as (3-subunits of ion channel protein by associating with a-subunits to form stable different physiological functions of potassium channels in heterologous polymer, which modulate their properties. KCNE 1、KCNE2 are widely dispersed in myocardium, participating the regulation of properties of voltage-gated cation channels and affecting the repolarization ofⅡ>Ⅲphases of active potential. Abnormal expressions of them will influence the physiological nature of ion channels. Previous studies have shown that abnormal expression of KCNE gene can induce malignant ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, cardiac long QT syndrome, but it is still a hot debate on whether abnormal expression of KCNE gene is associated with arrhythmia after AMI.Application ofβ-blockers can reduce the incidence of arrhythmias in the early stage of AMI, but the mechanism of antiarrhythmic electrophysiological is not fully understood. However, no relevant research has ever been done and reported about the effect ofβ-blockers on the expression and distribution of KCNE 1 and KCNE2 after AMI.ObjectiveThe purpose of this study is to test the expressions of KCNE1 and KCNE2 in infarcted surrounding myocardium of post-AMI heart by Western Blotting and reverse transcriptase polymerase chain reaction (RT-PCR) via the establishment of AMI model, and to observe the dynamic change rule of their expressions and the intervention effects of bisoprolol for them, so to suply more theoretical foundations in mechanism of arrhythmia after AMI and antiarrhythmia.Methods40pcs healthy and mature male Sprague-Dawley (SD) rats were sampled. The weight and age of the rats are 200g-250g/pc and 8 weeks old respectively. Rats were anesthetized by injecting 10% chloral hydrate into abdomen after being weighted. AMI model of rats was induced by ligating the left coronary artery under the help of respirator and biological signal acquisition system. All the rats were randomly divided into four groups:the 24-hour group(n=10),1-week group (n=10),4-week group(n=10)and bisoprolol group(n=10).The sham operation groups (SH) as the control groups of 24-hour goup,l-week group and 4-week group were set up respectively(n=10 in each group). Bisoprolol group was given bisoprolol 0.5mg/kg/d by gavage for 4 weeks, and the other three groups were given the same amount normal saline. Then the fringe of infarction of the hearts of rats were rapidly excised in the organized times. The expressions of KCNE1 and KCNE2 mRNA and protein were detected by RT-PCR and Western Blotting respectively. The expressions of KCNE1 and KCNE2 in the fringe of infarction were detected by Immunochemistry.ResultsIn all the SH groups there were the expressions of KCNE1 and KCNE2 mRNA and protein, which were no significance in different groups (P>0.05). Compared with the SH group, the mRNA and protein expressions of KCNE1 and KCNE2 in 24-hour AMI group were increasing (P<0.05), and in the 1-week AMI group came up to the maximum. The mRNA and protein expressions of KCNE1 and KCNE2 were decreasing in 4-week AMI group and bisoprolol group, but they were higher than SH group (P<0.05), while the mRNA and protein expressions of KCNE1 and KCNE2 in bisorolol group were lower than in 4-week AMI group (P<0.05).The myocardial cells in SH group arranged in order, with no inflammatory cells infiltrating and the proliferation of fiber collagen tissue. The myocardial cells in the fringe of infarction arranged disorganized and had compensatory hypertrophy, with the inflammatory cells infiltrating and the proliferation of fiber collagen tissue. The change of bisoprolol group was between the SH group and the MI group.ConclusionsThere were the expressions of KCNE1 and KCNE2 mRNA and protein in the normal myocardial cells. After the acute myocardial infarction happened, the expressions of KCNE1 and KCNE2 mRNA and protein were changing dynamically in the fringe of infarction in different times. The reasons for this may be accorded to a series of the pathological factors, such as sympathetic hyperfunction, renin angiotensin activated, ischemia, anoxia, ischemia reperfusion injury, metabolic disturbance and so on. The expressions of KCNE1 and KCNE2 mRNA and protein in the myocardial infarction tissues were increased, but they were inhibited in bisoprolol group. |
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