The Study On The Expression Of Sodium Hydrogen Exchanger 1 In The Mice With Acute Viral Myocarditis And Its Relationship With Myocardial Collagen Remodeling

VMC is a common cardiovascular disease in pediatrics. The incidence is rising in recent years.It is not rather rare that some cases occurs sudden death; and chronic myocarditis leads to dilated cardiomyopathy (DCM). These demonstrate that VMC has greatly threatened children's health and the quality of life. However, the pathogenesis of VMC is not clarified thoroughly and sometimes the therapy is not effective. So it is very important to illuminate the mechanism of VMC.The myocardial sodium-hydrogen exchanger subtype 1(NHE-1) which is an ion exchanger protein is distributed throughout the mammalian cell membrane. It extrudes protons concomitantly with Na influx in a 1:1 stoichiometric relationship thereby regulating cytosolic pH (pHi) and cell volume etal. Previous research indicates that NHE-1 can increased and expressed activitly in the process of myocardial fibrosis responses to various stimuli in cardiac cells, NHE-1 inhibitors can block it. The number of studies indicate that myocardial fibrosis exist in different periods of VMC. Some studies also demonstrate that the development of myocardial fibrosis of the pathogenesis of viral myocarditis is one of the important reasons in the VMC arrhythmia, cardiac dysfunction and even cardiac sudden death; which can affect the course of disease and prognosis in children. So, we hypothesized that NHE-1 may play an important role in the pathogenesis of VMC.This study establishes VMC models through Balb/c mice infected with coxsackievirus B3 (CVB3). We selected male BALB / c mouse, which were randomly divided into 2 groups: control group 35, VMC Group 50, and recorded the general symptoms of the mice and the death. After virus inoculation, we weighed the mice, determined the value of CK-MB in blood serum, examined the score for myocardial necrosis and cellular infiltration, observed myocardial collagen fiber distribution in mice, and measured CVF. Furtherly, the contents of NHE-1 wase detected in immunohistochemical techniques and reverse transcription polymerase chain reaction and the correlations were analyzed.The results showed that: the mortality of VMC mice is significantly increased. The value of CK-MB increased at the fourth day post infection, then the value was increased continuously, and the value of CK-MB was climbed a peak at the 7th days post infection. The value was closed to normal at the 28 th day. the score for myocardial necrosis and cellular infiltration have the same regular pattern.The contents of NHE-1 in VMC group were higher than that of control group, and this trend were enhanced with the disease development. It suggested that NHE-1 may be involved in process of VMC.CVF can assess the proportion and degree of interstitial fibrosis as a objective indicator. In this study, we found that CVF increased significantly after 14th days post infection in VMC group. Linear correlation analysis showed the contents of NHE-1CTGF with CVF was negative correlation remarkably. It suggested that NHE-1may be involved in process of VMC.NHE-1protein expression were significantly enhanced around the myocarditis syndrome and necrotizing lesions. It suggested that inflammatory stimulation may be related to NHE-1 abnormal expression. Furtherly, the gray value of NHE-1 protein and myocardial pathologic score for linear correlation analysis showed r = 0.0027, P<0.05, it is no correlation between them. And then, the NHE-1 protein and cardiac enzyme CK-MB linear correlation between the analysis showed r = 3.5274, P <0.05, no correlation between the two. The expression of NHE-1in Viral myocarditis and inflammatory stimuli have no obvious correlation.On the basis of recent research, this experiment further studies the role of NHE-1 in the pathogenesis of VMC. Thus we hope that NHE-1will become the therapeutic target for myocardial fibrosis someday. The future work will develop the approach to prevent myocardial fibrosis by means of NHE-1, such as to block the expression of NHE-1 by using NHE-1 inhibitor, Such as amiloride or more specific drug-cariporide and other drugs. Also, we should further explore how the NHE-1 involved in the pathogenesis of VMC. Thus VMC may be treated more effectively.