卡托普利对病毒性心肌炎小鼠NF-κB活化及MCP-1表达的影响

Effects of captopril on the activation of NF-kB and the expression of MCP-1 in murine viral myocarditis

目的探讨核因子kB(NF-kB)活化在病毒性心肌炎发病机制中的作用及卡托普利对NF-kB活化的调节作用。方法55只Balb/c小鼠随机分为3组:柯萨奇病毒B3(CVB3)感染组、CVB3感染加卡托普利治疗组和对照组,分别在实验的第7、14和21天处死动物,留取血清、心肌标本,免疫组化检测心肌组织中NF-kB活化和单核细胞趋化蛋白-1(MCP-1)表达,双抗体夹心ELISA法检测血清MCP-1含量。结果感染组小鼠心肌组织中NF-kB活化、MCP-1表达较对照组明显增强(P<0.01),而且与心肌病变程度相关;与对照组比较感染组小鼠血清MCP-1含量明显增加(P<0.001);治疗组心肌组织中NF-kB活化、MCP-1表达及血清MCP-1含量均较感染组显著降低(P<0.05或P<0.01)。结论NF-kB活化在病毒性心肌炎发病机制中发挥重要作用,抑制NF-kB活化可能是卡托普利治疗病毒性心肌炎的作用机制之一。

Objective To investigate the role of nuclear factor kappa B(NF-kB) in the pathogenesis of viral myocarditis and the regulation effect of captopril on the activation of NF-kB in vivo. Methods Fifty-five male Balb/c mice were randomly divided into three groups: the Coxsackievirus B3 (CVB3) infected group, the CVB3 infected and captopril-treated group, and control group. They were killed on days 7, 14 and 21 respectively. The immunohistochemical studies and medical imagine analysis were performed to evaluate the activation of NF-kB and the expression of MCP-1 in myocardial tissue. Serum MCP-1 levels were assayed with ELISA. Results The significant up-regulation of NF- kB activation and MCP-1 expression level were observed in the myocardial tissue of infected mice in comparison with control group(P<0.05) . NF-kB activation and MCP-1 expression levels correlated positively with the severity of the myocardial tissue injury. The up-regulation of MCP-1 expression levels was positively correlated with NF-kB activation in infected group (r = 0. 685,P<0. 05). Serum MCP-1 levels in infected group were markedly increased in comparison with control group(P<0. 001). Significant down-regulation of NF-kB activation and MCP-1 expression was observed in captopril-treated group. Conclusions The activated NF-kB might play an important pathogenic role in viral myocarditis and the therapeutic effect of captopril might be mediated through the suppression of NF-kB activation.