辛伐他汀对急性病毒性心肌炎小鼠心肌病变的影响

Effect of simvastatin on myocardial pathological changes in mice with acute viral myocarditis

目的观察辛伐他汀对急性病毒性心肌炎(VMC)小鼠的心肌病变和肿瘤坏死因子-α(TNF-α)表达的影响。方法给BALB/c小鼠腹腔接种柯萨奇病毒B组3型(CVB_3)病毒建立急性VMC模型。随机均分为模型对照组、辛伐他汀5mg·kg^(-1)·d^(-1)治疗组(5mg组)、20mg·kg^(-1)·d^(-1)治疗组(20mg组)及40mg·kg^(-1)·d^(-1)治疗组(40mg组)。用药14d后,观察各组小鼠的心肌病理改变和死亡率,采用实时定量聚合酶链反应检测心肌中TNF-αmRNA表达水平,酶联免疫吸附试验检测血清TNF-α水平。结果模型对照组的心脏病变积分、心肌TNF-αmRNA表达和血清TNF-α水平分别为(2.84±0.62)分、0.139±0.029和(147.4±13.3)ng/L,5mg组分别为(2.48±0.55)分、0.124±0.026和(139.0±20.2)ng/L,20mg组分别为(1.56±0.58)分、0.057±0.012和(113.0±11.8)ng/L,40mg组分别为(1.61±0.62)分、0.051±0.012和(101.3±13.8)ng/L,20mg和40mg组均显著低于模型对照组(P值均<0.01),5mg组与模型对照组的差异均无统计学意义(P值均>0.05)。各组间小鼠死亡率的差异均无统计学意义(P值均>0.05)。结论辛伐他汀可减轻急性VMC小鼠心肌炎症和心肌病变程度,其机制部分与减少TNF-α表达有关。

Objective To investigate the effect of simvastatin on myocardial histopathologic changes and expression of tumor necrosis factor-α （TNF-α） in mice with acute myocarditis caused by coxsackievirus B3. Methods BALB/c mice were intraperitoneally inoculated with Coxsackievirus B3 virus to create myocarditis model, then the mice were divided into model group, simvastatin 5 mg · kg^-1 · d^-1 treated group（5 mg group）, 20mg· kg^-1 · d^-1 treated group（20 mg group）, and 40 mg · kg^-1 · d^-1 treated group（40 mg group）. Myocardial histopathologic changes and mortalities of mice in each group were observed 14 days later. Myocardium TNF-α mRNA expression was determined by real-time RT-PCR and the serum TNF-α levels were assayed using ELISA. Results The pathological score, myocardium TNF-α mRNA expression, and serum TNF-α level in model group were 2.84 ± 0. 62, 0. 139 ± 0. 029, and （147.4 ± 13.3） ng/L, respectively; in 5 mg simvastatin group were 2.48 ± 0.55, 0. 124 ± 0.026, and （139.0 ± 20. 2） ng/L, respectively; in 20 mg simvastatin group were 1.56 ± 0. 58, 0.057 ± 0. 012, and （113.0 ± 11.8） ng/L, respectively; and in 40 mg simvastatin group were 1.61 ± 0.62, 0.051 ± 0.012, and （101.3 ± 13. 8） ng/L, respectively. The above 3 parameters in 20 mg and 40 mg simvastatin group were significantly lower than those in the model group（all P 〈 0.01）; there was no significant difference between 5 mg simvastain group and model group. The mortalities of mice were not significantly different between all the groups. Conclusion Simvastatin can relieve acute inflammation and cardiomyopathy degree in mice with VMC, partially due to the down-regulation of TNF-α mRNA expression and serum TNF-α level. （Shanghai Med J, 2007, 30..765-769）