Effect of carvedilol on expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 in murine viral myocarditis

Abstract

Objective To investigate the role of tumor necrosis factor-α(TNF-α) and monocyte chemoattractant protein-1(MCP-1) in the pathogenesis of viral myocarditis(VMC) and the effect of carvedilol. Methods Eighty male Balb/c mice were randomly divided into 3 groups: control group(n=20), myocarditis group(n=30) and carvedilol group(n=30). The latter 2 groups were intraperitoneally inoculated with Coxsackie virus B3(CVB3) to induce VMC, while control group with virus-free Eagle's medium instead.Carvedilol was poured 5 mg/kg from the next day after injecting virus in carvedilol group, 9 g/L saline was used in control group and myocarditis group, twice a day.On the 7th and 14th day after inoculation, 8 mice were sacrificed after taking blood sample which were randomly selected from each group.Histological cross sections of hearts were stained with hematoxylin-eosin(HE), and the content of serum TNF-α was assayed with enzyme-linked immunoadsordent assay, while the expression of MCP-1 mRNA in myocardial tissue was detected with reverse transcriptase-polymerase chain reaction(RT-PCR) method. Results The pathological score of myocarditis group was significantly higher than that in control group(P<0.01), while carvedilol group was significantly lower than that in myocardial group(P<0.05). The serum level of TNF-α of VMC mice in myocarditis was significantly higher than that in control group(P<0.01) and positively correlated with the pathological score of the myocardium(r=0.42, P<0.05), and serum TNF-α in carvedilol group was remarkably decreased compared with myocarditis group(P<0.05). The expression level of MCP-1 mRNA in myocarditis group was increased significantly compared with control group(P<0.01), and remarkably decreased in carvedilol group compared with myocarditis group(P<0.05). Conclusions TNF-α and MCP-1 may be involved in the pathogenesis of VMC, and carvedilol may protect myocardium against CVB3-induced VMC by down-regulating the expression of TNF-α and MCP-1. Key words: Carvedilol; Viral myocarditis; Tumor necrosis factor-α; Monocyte chemoattractant protein-1