Experimental Study Of Function Of Connective Tissue Growth Factor And Effects Of Shenmai Injection In Viral Myocarditis

Now, viral myocarditis(VMC) has become one of the more common diseases in children. Virus infection can not only cause the degeneration and necrosis of myocardial cells, but also generate endocarditis, pericarditis and inflammatory lesion of other organs. Thus viral myocarditis can be considered as a kind of independent disease, as well as a part of systemic infection. Moreover continuing viral infection often results in dilated cardiomyopathy. They are the important roots of sudden cardiac death. This shows that viral myocarditis have a serious impact on the child's physical health. Therefore, how to illuminate the pathogenesis and the treatment of VMC has a certain theoretical and practical significance.Recent studies show that cytokines are closely related with the occurrence and development of VMC. CTGF(connective tissue growth factor) is a kind of cytokines found by recent studies, which exists widely in multiple tissues and organs of human body, and plays important role in the process of fibrosis and tissue injury. It has many biological activities, which contain the promotion of cell proliferation, collagen synthesis, extracellular matrix synthesis, and induction of apoptosis and the promotion of angiogenesis.TGF-βis an important regulator of CTGF cytokines. TGF-β₁ can increase protein synthesis in interstitial, then make extracellular matrix over-expression. It can also stimulate the protease inhibitors and promoting fibrosis. It has been confirmed that CTGF and TGF-βplay an important role in fibrotic diseases. At the same time, the study found myocardial fibrosis plays an vital role in the process of the development of VMC to DCM.This research successfully establishes the models of viral myocarditis through BALB/C mice infected with coxsackievirus B3. After virus inoculation, we weighed the mice, examined the score for myocardial necrosis and cellular infiltration, observed myocardial collagen fiber distribution in mice, measured CVF and the value of CK-MB in blood serum. At the same time, the contents of TGF-β₁ and CTGF were detected in immunohistochemical techniques and reverse transcription polymerase chain reaction and the correlations were analyzed. Then the therapeutic effect of ShenMai injection for viral myocarditis were discussed.The results showed that the mortality increased significantly in VMC group, and Shenmai injection can improve the survival rate of VMC mice. 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 between the 7th and 14th days post infection. The value was closed to normal at the 21 st day. While the value of CK-MB and the score for myocardial necrosis and cellular infiltration significantly reduced in treatment group. The results showed that Shenmai injection can effectively improve the situation of myocardial ischemia, the prevention of myocardial cell damage and reduce myocarditis.The contents of CTGF and TGF-β₁ in VMC group were higher than that of control group, and this trend were enhanced with the disease development. CTGF and TGF-β₁ protein expression were significantly enhanced around the myocarditis syndrome and necrotizing lesions. It suggested that inflammatory stimulation may be related to CTGF and TGF-β₁ abnormal expression. Linear correlation analysis showed the contents of CTGF with the contents of TGF-β₁ was positive correlation remarkably.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 CTGF with CVF was negative correlation remarkably. It suggested that CTGF may be involved in process of VMC. CTGF is an important role in the process of myocardial fibrosis, and this effect was executed in help of TGF-β₁.The contents of CTGF and TGF-β₁ in treatment group were lower than that of VMC group. It suggested that Shenmai injection can effectively reduce the extent of myocardial fibrosis. Shenmai injection can prevent myocardial fibrosis in the process of VMC mice. In this study, the reason of Shenmai injection can inhibit myocardial fibrosis maybe reduce the peroxide level in vivo.On the basis of recent research, this experiment further studies the role of CTGF in the pathogenesis of VMC. Thus we hope that CTGF will become the therapeutic target for myocardial fibrosis someday. The future work will develop the approach to prevent myocardial fibrosis by means of CTGF, such as to block the expression of CTGF by using the antibody or to inhibit the activity of CTGF. Thus VMC can be treated more effectively.