阿托伐他汀的不同用药方式对心肌缺血再灌注损伤的影响及机制

Effects of different administrations of atorvastatin on myocardial ischemia/reperfusion in rats

目的探讨阿托伐他汀的不同用药方式对心肌缺血/再灌注(myocardial ischemia/reperfusion,MI/R)损伤的影响及机制。方法建立SD大鼠在体MI/R模型。160只大鼠随机分为MI/R组、MI/R+阿托伐他汀常规剂量(MI/R+N)组、MI/R+术前单次负荷剂量(MI/R+SL)组、MI/R+术前连续负荷剂量(MI/R+ML)组,并设假手术(Sham)组。Evans blue/TTC双染色测定心肌梗死面积;检测心肌ATP酶活性及血清白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平;小动物超声测定左室射血分数(LVEF%)。结果与MI/R+N组比较,MI/R+SL组和MI/R+ML组的心肌梗死面积明显减少(P<0.05),心肌ATP酶活性明显增高(P<0.05),血清IL-6和TNF-α水平明显减低(P<0.05),MI/R后24hLVEF%显著改善(P<0.05)。而MI/R+SL组和MI/R+ML组间的心肌梗死面积、心肌ATP酶活性、IL-6和TNF-α水平、LVEF%的差异无统计学意义。结论负荷剂量阿托伐他汀可通过改善心肌ATP代谢,减少炎症因子异常表达等机制,减轻MI/R损伤。术前单次负荷剂量与术前连续负荷剂量的用药方式对保护MI/R无差别。

Objective To study the effects and mechanism of different administrations of atorvastatin on myocardial ischemia/reperfusion(MI/R)in rats.Methods A total of 160 male SD rats were randomly divided into five groups:sham group,MI/R group,atorvastatin of conventional dose(MI/R+N)group,atorvastatin of preoperative signal loading dose(MI/R+SL)group,and atorvastatin of preoperative continuous loading dose(MI/R+ML)group.MI/R model was established in the rats.Myocardial infarction size was detected by Evans blue/TTC staining.The activity of ATPase of cardiac muscle and the levels of serum IL-6 and TNF-αwere detected by ELISA.The level of LVEF% was detected by small animal ultrasound.Results Compared with MI/R+N group,MI/R+SL and MI/R+ML groups had significantly smaller myocardial infarction size(P<0.05),higher activity of ATPase(P<0.05),lower levels of serum IL-6 and TNF-α(P<0.05),and more advanced LVEF%(P<0.05).However,MI/R+SL group and MI/R+ML group did not differ significantly in the above-mentioned parameters.Conclusion Atorvastatin of loading dose might alleviate MI/R injury by improving ATP metabolism of cardiac muscle and reducing abnormal expressions of inflammation factors.Meanwhile,the administration of preoperative continuous loading dose and preoperative signal loading dose of atorvastatin may not differ in protecting against MI/R injury.