肿瘤坏死因子-α单抗对小鼠病毒性心肌炎的影响

Effect of anti-TNF-alpha monoclonal antibody on viral myocarditis in mice

摘要:

目的：探讨细胞间粘附分子-1(ICAM1)及肿瘤坏死因子α(TNFα)在心肌炎发病中的作用及TNF-α单克隆抗体预处理对其的影响,为临床治疗提供实验依据。方法：Balb/c雄性小鼠随机分为三组:正常对照组、柯萨奇B3病毒感染组和病毒感染加TNFα抗体干预组,采用光镜、电镜和免疫组织化学测定不同时期心肌病理变化、超微结构改变和心肌ICAM1与TNFα的表达。结果：光镜和电镜结果显示干预组心肌病理变化和超微结构改变较感染组减轻;免疫组织化学结果显示干预组ICAM1及TNFα的表达较感染组减轻(7d:14.71±1.94vs18.80±2.62,P<0.01和16.70±2.90vs20.63±1.95,P<0.05;14d:17.49±2.58vs23.51±3.50,P<0.01和19.29±3.21vs24.64±2.97,P<0.01);感染组TNFα与ICAM1的表达呈正相关(r=0.706,P<0.05),TNFα,ICAM1的表达与心肌病变积分呈正相关(r=0.737,P<0.05;r=0.693,P<0.05)。结论：TNFα与ICAM1在病毒性心肌炎小鼠的发生发展中发挥重要作用,抗TNFα单克隆抗体抑制其表达,对受损心肌有保护作用。

Abstract:

OBJECTIVE: This study was aimed to investigate the expressions of ICAM-1 and TNF-α in viral myocarditis and the effect of anti-TNF-alpha monoclonal antibody on viral myocarditis in mice. METHODS: Sixty-six male Balb/c mice were randomly assigned into an Infection group (n=30), an Intervention group (n=18) and a Normal control group (n=18). The Infection and Intervention groups were inoculated intraperitoneally with 0.2 mL TCID50 10~ -6/mL coxsackie B_3(CVB_3) solution. Anti-TNF-amAb [0.1 mL/(kg.d)] was additionally administered starting at 1 day before CVB_3 virus inoculation until day 5 in the Intervention group. On the 7th and 14th days after virus inoculation, the changes of histopathology and ultrastructure of myocardium were studied with light and electron microscopy. The expressions of ICAM-1 and TNF-α were detected by immunohistochemical method. RESULTS: Myocardium histopathology of mice in the Normal control group was normal. Myocardial necrosis and cellular infiltration were more prominent in the Infection group than in the Intervention group.ICAM-1 and TNF-α were expressed in the myocardium of Normal control gorup at a very low level, which were significantly lower than those in the Infection and Intervention groups. The expressions of ICAM-1 and TNF-α were dramatically reduced in the Intervention group compared with those in the Infection group.In the Infection group, a positive correlation was found between the expressions of ICAM-1 and TNF-α ( r=0.706, P<0.05); and both ICAM-1 expression and TNF-α expression were positively related to pathological scores of myocardium (r = 0.737, P<0.05;r = 0.693, P<0.05). CONCLUSIONS: ICAM-1 and TNF-α may play important roles in the pathogenesis of viral myocarditis. Anti-TNF-alpha monoclonal antibody has protective effects on myocardial tissues by inhibiting the ICAM-1 and TNF-α expression.