| Viral myocarditis (VMC) is a common cardiovascular disease. In China, VMC cases have been increasing year after year. VMC has become one of the main causes of sudden unknown death events in teenagers. Moreover chronic VMC often results in dilated cardio-myopathy. These demonstrate that VMC has greatly threatened human health. However, up to now, the mechanism of VMC has been nuclear, which leads to the lack of effective treatments of VMC. So it has importantly theoretic and practical significance to illuminate the mechanism of VMC and provide the effective treatment.It is known that viral infection is an important pathogen of VMC, and VMC caused by coxsackievirus group B type 3 (CVB3) infection accounts for more than fifty percent VMC cases. Previous studies showed that cytokines play a very complex role during the process of viral myocarditis, and possess different activity in different period. Most of them can be induced or inhibited by themselves or others. It is well known that indirect immunological injury in VMC is associated with the infiltration of a great amount of inflammatory cells. The infiltration of inflamma tory cells is one of characteristic pathological changes in VMC.Generally, the infiltration of inflammatory cells is a complex and multiple- stepped process involved in many cells and molecules. Induced by inflammatory signals and cell-adhesion molecules, various inflammatory cells accumulate in the site of infection. The process consists of rolling, adherence, extravasation and so on. It has been confirmed that NFκB play a vital role in many cardiovas- cular diseases such as artherosclerosis, heart failure, myocardial ischemia- reperfusion. Nora Goren study showed activation of NFκB in cardiomyocytes has been shown to be an important mediator of the inflammatory response in the heart and of organ damage, According to above, we hypothesized that NFκB may play a vital role in the pathogenesis of myocarditis and SB203580 may reduce the inflammation of VMC through resisting the activity of NFκB.Therefore, In the study, we classify the mice into three groups:⑴normal group;⑵virus group;⑶(SB203580)treating group. we first established VMC models through BALB/c mice infected with coxsackievirus B3, and then SB203580 were injected to the mice of interfering group until day 4, after virus inoculation until day 0, 4, 7, 10, we examined (1) the contents of NFκB mRNA and NFκB protein in the cadiocyte nucleus; (2) Virus titers of hearts; (3) Score for myocardial necrosis and cellular infiltration; ( 4) the contents of serum TNF-α. Based on the results, we further studied the resisting effects of SB203580 to CVB3 infection time in NFκB mRNA and NFκB protein of the cadiocyte nucleus and score for myocardial necrosis and cellular infiltration, degree of relationship of the in NFκB of the cadiocyte nucleus and score for myocardial necrosis and cellular infiltration. Our study would provide new theoretic base and experimental evidence for the prevention and therapy of SB203580 to VMC.The contents of NFκB mRNA and NFκB protein in the cadiocyte nucleus was detected at the 0, 4th, 7th and 10th day posty CVB3 infection quantitatively by RT-PCR and the western-blot. The results showed that the contents of NFκB mRNA and NFκB protein in the cadiocyte nucleus increased slightly at the forth day post infection, then both was increased continuously, and climbed a peak at the 10th day post infectionin in virus group , the contents of NFκB mRNA and NFκB protein in treating group were reduced continuously at 7th and 10th day,and was lower than that of virus group at the same day.The level of TNF-αin blood in virus group of mice withViral myocarditis at 4th, 7th and 10th are higher than that in control group, the level of TNF-αin blood in treatment group at 7th and 10th are lower than that in control group.CVB3 infectivity was found (TCID50 was 103.48) at the 4th day post infection in myocardial tissue, that in treating group was not different than virus group, then TCID50 increased at the 7th day ( 104.16), and at 10th day TCID50 reduced to 103.68, and the TCID50 at 7th, 10th day were lower than that of the virus group at the same time. It indicated that CVB3 infection influenced the NFκB in loading-independent manner in vivo. At the same time analyzing score for myocardial necrosis and cellular infiltration, linear correlation analysis showed Virus titers of hearts and myocardial necrosis is positive correlation remarkably (r=0.964, 0.899) at 7th, 10th day post infection. The contents of NFκB in the cadiocyte nucleus and myocardial necrosis, cellular infiltration is positive correlation remarkably ( r=0.947, 0.925).In summary, we found that SB203580 could reduce the injury of the VMC mice cardiacyte nucleus ,the most important reason was resisting the activity of NFκB and further resisting the cytokines for example TNF-αand so on. Linear correlation analysis showed virus replication in the cardiocyte is important in early phase of pathologic development, NFκB play a vital role in the regulation of inflammatory cell infiltrate myocardium and pathogenesis of myocarditis. To interfere in activation of NFκB may reduce the aggression to myocardium by Immune effector cell, attenuate inflammatory cell infiltrate myocardium and myocardial necrosis, sustain its integrity of structure and function. The study has elucidated the role of NFκB in pathogenesis of VMC, providing a potential pathway in prevention and therapy of VMC and giving a new treatment idea to research on other inflammatory related diseases. |
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