ABSTRACT
Objective: To determine the effect of proteasome inhibitor MG-132 in mice with an inflammatory reaction of acute viral myocarditis induced by coxsackie virus B3 (CVB3) infection.
Methods: BALB/C mice were intraperitoneally inoculated with CVB3 to induce myocarditis. Twenty-four hours after infection, MG-132 was administered at a dose of 0.5 mg/kg or 1 mg/kg for seven days by intraperitoneal injection. Normal controls were treated with the same volume of dimethyl sulfoxide. The changes in myocardial ultrastructure, the protein levels of IL-6 and TNF-α, the number of PMN, and survival rate of each group were documented.
Results: Compared with the normal group, the protein levels of IL-6 and TNF-α, and the number of polymorphonuclear leucocytes (PMN) were significantly increased in CVB3 group (p < 0.05). The cardiocytes were diffusely and swollen, the myofilaments were lysed, and the mitochondria swollen and vacuolized. The above-mentioned inflammatory factors of the MG-132 group were significantly decreased when compared with the CVB3 group (p < 0.05). The degree of damage of cardiocytes in MG-132 group was less and the mortality due to deadly arrhythmia was lower than that in CVB3 group.
Conclusion: These results show that MG-132 protects mice from CVB3-induced acute viral myocarditis through suppressing the expression of inflammatory factors. Our research provides further evidence that the ubiquitin-proteasome system is a potential target therapy for viral myocarditis.
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