辛伐他汀对BALB/c小鼠病毒性心肌炎急性期的作用及其机制

目的:研究辛伐他汀对小鼠病毒性心肌炎急性期的作用及其机制。方法:应用柯萨奇B3病毒制作BALB/c小鼠病毒性心肌炎模型,辛伐他汀混悬液灌胃,按辛伐他汀剂量不同分为1mg/kg组、10mg/kg组及100mg/kg组,并设正常对照组及病毒对照组,7d后观察心肌组织病理学改变、血清白细胞介素6(IL-6)水平、心肌组织中肿瘤坏死因子α(TNF-α)表达水平,并做心肌组织中病毒滴度检测。结果:辛伐他汀1mg/kg组各检测指标较病毒对照组无显著性改变(P>0.05)。辛伐他汀10mg/kg组及100mg/kg组心肌组织损伤程度较病毒对照组均明显减轻(P<0.05)、心肌组织中病毒滴度显著性增高(分别为P<0.05,P<0.01)、IL-6和TNF-α水平明显降低(分别为P<0.05,P<0.01);辛伐他汀100mg/kg组与10mg/kg组比较,各检测指标差异显著(P<0.05)。心脏重/体重各组间差异不具有显著性(P>0.05)。结论:辛伐他汀在小鼠病毒性心肌炎急性期对心肌具有保护作用,呈剂量依赖性。这种作用可能与IL-6、TNF-α水平降低而免疫损伤减弱有关。应用辛伐他汀后病毒性心肌炎小鼠清除病毒的能力减弱,但没有导致病毒性心肌炎急性期心肌损伤加重。

Simvastatin's Protective Effect and Its Mechanism in Acute Period of Viral Myocarditis Caused by CVB3 in Mice

Objective: To investigate the effect of simvastatin on the expression of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and its mechanisms in mouse viral myocarditis VMC caused by coxsackievirus B3(CVB3). Methods: Sixty male BALB/C mice aged four weeks were involved and divided into five groups randomly and equally as normal control group, viral control group, oral administration of simvastatin 1 mg/kg group, 10 mg/kg group, and 100 mg/kg group, and the last four groups were inoculated intraperitoneally with 0.2 ml of CVB3(Nancy strain). Normal control mice were inoculated intrapritonealy with 0.2 ml of Eagle's solution. Viral control group and normal control group were administrated with starch solution everyday. All mice were sacrificed at 7th day. Histological cross sections of hearts were stained with hematoxylin-eosin and myocardial histopathologic scores were counted under optical microscope. Viral titer was determined according to plaque-counting technique. The levels of TNF-α in myocardial tissue and serum IL-6 were assayed by immunohistochemical stain and ELISA respectively.Results: ① The grade of myocardial necrosis in 100 mg/kg group and 10 mg/kg group was significantly lower than in viral control group(P<0.05 respectively). There were no significant differences between the 1 mg/kg group and viral control group (P>0.05). ② The levels of viral titers, IL-6 and TNF-α in 100 mg/kg group and 10 mg/kg group were significantly lower than in viral control group(P<0.01 and P<0.05 respectively), and there were the same result in 100 mg/kg group compared with 10 mg/kg group (P<0.05). The level of IL-6 and TNF-α in normal group was lower than in viral control group(P<0.01), and lower than in 10 mg/kg group and 100 mg/kg group also (both P<0.05). ③There was no significant difference in heart/body weight ratio among the five groups. Conclusion: Simvastatin could reduce the myocardial necrosis in VMC mice infected by CVB3 in acute period and this function positively correlated with the dose of simvastatin. The properties of anti-inflammatory of simvastatin may play a key role in this process. The anti-viral effect in VMC mice would decrease after administration of simvastatin, but this result wouldn't deteriorate the VMC in the acute period.