Immunoregulatory Effect Of Simvastatin On Acute Coxsackie Virus B₃ Murine Myocarditis

Objective To explore the Immunoregulatory effect of simvastatin, 3-hydroxy-3-methy-glutary coenzyme A(HMG-COA) reductase inhibitor, on the expression of MHCâ…¡molecules on acute coxsackie virus B₃ murine myocarditis, and to explore the therapeutic potential for VMC.Methods Seventy five male Balb/c mice were divided into five groups randomly(n=15). Mice in normal control group, viral control group, oral administration of simvastatin 1mg/kg group, 10 mg/kg group, and 100mg/kg group, were inoculated intrapritoneally with 0.4ml of CVB3(Nancy strain). Normal control group and were inoculated intraprionealy with 0.4 ml distilled water. All the mouse were sacrificed on day 14. the severity of myocarditis was evaluated histopathologically. Immnuohistochemistry techniques was used to distinguish the CD4⁺ or CD8⁺T lymphocytes and evaluate the expression of MHC-â…¡,MMP-3 and MMP-9 in myocardium.Results Compared with viral control group, there were no significant changes in all indices observed in the lmg/kg simvastatin group(P＞0.05); in the 10mg/kg/d and 100mg/kg/d simvastatin group, the expression of MHC-â…¡,MMP-3 and MMP-9 significantly decreased(P＜0.05, respectively), the grade of myocardial necrosis was significantly decreased(P＜0.05, respectively), the expression of MHC-â…¡,MMP-3 and MMP-9 was significantly lower than in 10mg/kg/d group.Conclusion Simvastatin exert a protective effect on acute coxsackie virus B₃ murine myocarditis, which is mediated by depressing the expression of MHC-â…¡and activation of CD4⁺ T.