ABSTRACT

Objective: To determine the effects of proteasome inhibitor MG-132 on mice with an inflammatory reaction to acute viral myocarditis induced by coxsackie virus B3 virus (CVB3) infection.

Methods: BALB/C mice were intraperitoneally inoculated with CVB3 to induce myocarditis. Twenty-four hours after the 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 DMSO. The changes of myocardial ultrastructure, the protein levels of IL-6 and TNF-α, the number of polymorphonuclear leucocytes (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 PMN were significantly increased in the CVB3 group (p < 0.05). The cardiocytes were diffusely swollen. The myofilament was lysed, and the mitochondria swelled and vacuolizated. The above-mentioned inflammatory factors of MG-132 groups were significantly decreased when compared with the CVB3 group (p < 0.05). The degree of the damage of the cardiocytes in the MG-132 group was less and the mortality due to deadly arrhythmia was lower than that in the CVB3 group.

Conclusion: The results showed that MG-132 protected the mice from CVB3-induced acute viral myocarditis by suppressing the expressions of the inflammatory factors. Our research provides further evidence that the ubiquitin-proteasome system is a potential target therapy for viral myocarditis.