静注免疫球蛋白对病毒性心肌炎小鼠的疗效及机理研究

目的:探讨静注免疫球蛋白(intravenous immunoglobulin,IVIG)对病毒性心肌炎的疗效及其机理。方法:320只5周龄雄性BALB/c小鼠随机分为8组,感染组腹腔接种柯萨奇B3病毒(CVB3)制成心肌炎动物模型,在接种病毒后3、7 d分别腹腔注射IVIG(500 mg/kg.d-1)5 d和10 d,流式细胞仪定量检测心肌细胞凋亡率和坏死率,与心肌病理组织学积分和病毒滴度进行相关分析,并与中药黄芪疗效对比。结果:静注免疫球蛋白治疗组小鼠心肌内病毒滴度、心肌病理积分和心肌细胞凋亡率与坏死率明显低于病毒对照组和黄芪治疗组,以早期(感染后3 d)长程(10 d)治疗组效果最好。结论:静注免疫球蛋白通过抑制柯萨奇B3病毒,降低心肌细胞凋亡率和坏死率对病毒性心肌炎发挥疗效,其疗效高于传统中药黄芪。

Effect and mechanism of intravenous immunoglobulin on mice with viral myocarditis

Objective: To explore the effect and mechanism of intravenous immunoglobulin (IVIG) on mice with viral myocarditis. Methods: Three hundred and twenty male BALB/c mice, five weeks old, were divided into eight different groups randomly, including normal control, IVIG control, virus control, early IVIG short course treatment group, early IVIG long course treatment group, middle IVIG short course treatment group, middle IVIG long course treatment group and huangqi treatment group. Each mouse in infected groups was inoculated 0.1 ml CVB3 (TCID50 108/ml) intraperitoneally, and was given IVIG (500 mg/kg.d-1) intraperitoneally for five or ten days on the 3 rd or the 7 th day after infection respectively. Mouse in huangqi treatment group was given traditional Chinese medicine huangqi (30 mg/g) on 3 rd day after infection for ten days. Six mice in each group were killed on 7th, 14th, 21 st, 28 th day after infection separately, the virus liter in myocardium was examined, the percentage of apoptosis and necrosis of myocytes were detected by flow cytometry, and the myocardial histopathologic scores were counted under optical microscope. Results: (1) In treatment groups, the myocardial histopathologic scores, virus titer in myocardium and the percentage of apoptosis and necrosis of my-ocytes were lower than ihose in virus control group. All the items mentioned above in early IVIG treatment group were lower than those in middle IVIG treatment group and huangqi treatment group. Early IVIG long course group had the best effect; (2) In infected groups, the myocardial histopathological scores on 7 th day were positively correlated with virus titer in myocardium (r=0.96, P<0.01), no correlation was found on 14 th day; (3) The percentages of apoptosis and necrosis of myocytes on 7 th day were both positively correlated with virus titer in myocardium(r=0.94, P<0.01; r=0.76, P<0.01); (4) On 7 th and 14 th day, the percentages of apoplosis of myocyles were both positively correlated with myocardial hislopathological scores (r=0.92, P<0.01; r=0.84, P<0.01), the percentages of necrosis of myocytes were also positively correlated with myocardial histopathological scores (r =0.87, P<0.01; r=0.73, P<0.01). Conclusions: IVIG can reduce virus titer in myocardium and the percentage of apoplosis and necrosis of myocyles, so ameliorates the severity of myocardial lesions. It is good for viral myocarditis, especially used at early stage (3 rd day after infection) with longer course (500 mg/kg.d-1 for 10 days), and it is better than traditional chinese medicine huangqi.