Effects Of Drugs On A Mouse Model Of Viral Myocarditis

Objective:The goal of this study was to investigate the therapeutic benefits of atorvastatin on Coxsackie virus B3-induced myocarditis in Balb/c mice.Method:143 male 4-week-old Balb/c mice were divided into four groups randomly, including nomal control group (mice were administered Eagle's minimal essential medium 18 mice), virus group (virus solution intraperitoneally,3×103 PFU/mL,60 mice), atorvastatin control group (atorvastatin 10mg/kg/day,15 mice) and atorvastatin treatment group (virus plus atorvastatin 10mg/kg/day,50 mice). Atorvastatin was given 3 days after viral challenge and treatment lasted for 14 days in the atorvastatin control group and atorvastatin treatment group. Echocardiograms were examined on days 3,7, 10,14,21, and 30 after virus inoculation (same days for the atorvastatin control group). Blood samples were collected for cardiac troponin I detection at the same time. Myocardial inflammation, cell apoptosis and Fas expression were detected by histology and western blot, RT-PCR.Results:The myocardial histopathological score of mice in each infected group on day 7-10 after infection were significantly higher than that in normal control group, H&E staining and transmission electron microscopy revealed significant improvement of quantitative pathological features in the atorvastatin treatment group. Immunohistochemical microscopy also showed a marked decrease in the level of cardiac cell apoptosis in the atorvastatin treatment group compared to virus group that did not receive treatment (virus group:atorvastatin treatment group:12.36:4.82 P=0.006 at 14 days; 4.33:1.37 P=0.019 at 21days). The differences in cTnI values between the virus group and atorvastatin treatment group achieve statistical significance, there was decrease in cTnI in the atorvastatin treatment group(virus group:atorvastatin treatment group:3.62:1.65 P=0.042 at 7 days; 7.03:2.83 P<0.01 at 10 days; 6.30:2.20 P=0.034 at 14 days; 2.73:0.63 P=0.007 at 14 days 21 days). RT-PCR and western blotting revealed that the virus induced marked increases in Fas mRNA and protein expression, which could be prevented by treatment with atorvastatin.Conclusion:These results demonstrate that atorvastatin reduces the histological and functional severity of CVB3m-induced myocarditis, and inhibits apoptosis and Fas expression in the myocardium of CVB3m-infected mice. The therapeutic benefits of atorvastatin on myocarditis may be explained, at least in part, by inhibition of Fas expression and inhibition of cell apoptosis. Objective:The goal of this study was to investigate the therapeutic benefits of prednisone on Coxsackie virus B3m-induced myocarditis in Balb/c mice. Discussion the difference between different time of prednisone on viral myocarditis in mice at the medication.Method:303 male 4-week-old Balb/c mice were divided into eight groups randomly, including nomal control group(Mice were administered Eagle's minimal essential medium, n=18), prednisone group(Mice were administered prednisone(1mg/kg/day) at 3 days, n=15), infected control group(virus solution intraperitoneally,3×103 PFU/mL n=60), group of infected mice with prednisone treatment at early stage(Mice were administered prednisone(1mg/kg/day) at 3 days post-inoculation, n=50), group of infected mice with prednisone treatment at late stage(Mice were administered prednisone(1mg/kg/day) at 10 days post-inoculation, n=30), group of infected mice with prednisone treatment at early stage and Vit C(Mice were administered prednisone at 3 days post-inoculation and Vit C, n=50), group of infected mice with prednisone treatment at late stage and Vit C(Mice were administered prednisone at 10 days post-inoculation and VitC, n=30), group of infected mice with Vit C(Mice were administered VitC n=50). Prednisone was given 3 or 10days after viral challenge and treatment lasted for 14 days. The Echocardiograms were examined on days 3,7,10,14,21, and 30 after virus inoculation. Blood samples were collected for cardiac troponin?detection at the same time. Myocardial inflammation, cell apoptosis and Fas expression were detected by histology and western blot, RT-PCR.Results:The myocardial histopathological score of mice in each infected group on day 7-10 after infection were significantly higher than that in normal control group, but no significant difference in each infected group. On day 14 after infecteion, the myocardial histopathologic socre of mice with Prednisone treatment at early stage were significantly lower than that in other infected groups, H&E staining and transmission electron microscopy revealed significant improvement of quantitative pathological features in the prednisone treatement at early stage. Immunohistochemical microscopy also showed a marked decrease in the level of cardiac cell Apoptosis in the Prednisone-treated group compared to infected animals that did not receive treatment. The differences in cTnI values between the virus-challenged animals and prednisone -treated virus-challenged mice achieve statistical significance, there was a trend toward a decrease in cTnl in the Prednisone-treated mice.RT-PCR and western blotting revealed that the virus induced marked increases in Fas mRNA and protein expression, which could be prevented by treatment with Prednisone.Conclusion:Prednisone and vit c therapy at early stage ameliorated the severity of myocardial lesions in viral myocarditis, especially used in early stage of the disease. Prednisone and vit c therapy reduced the inflammatory infiltration in myocardium, inhibited autoimmune response. Prednisone therapy reduced the lever of serum cardiac troponin I in viral myocarditis. These results demonstrate that Prednisone and vit c reduces the histological and functional severity of CVB3m-induced myocarditis, and inhibits apoptosis and Fas expression in the myocardium of CVB3m-infected mice. The therapeutic benefits of prednisone on myocarditis may be explained, at least in part, by inhibition of Fas expression and inhibition of cell apoptosis.