辛伐他汀抑制大鼠急性心肌梗死后氧化应激的实验研究

摘要

Objective To establish the rat myocardial infarction model to observe the effects of different kinds of doses of simv-astatin for inhibiting the oxidative stress after myocardial infarction ,and to explore the potential mechanism of different doses of simvastatin for improving the rat ventricular remodeling and cardiac function .Methods The coronary artery anterior descending branch was ligated for establishing the myocardial infarction rat model and the different doses of simvastatin (20 ,40 ,60 mg · kg -1 · d-1 ) were given for intervention .After 4 weeks ,the cardiac ventricular remodeling indicators ,superoxide dismutase(SOD) and cop-per zinc superoxide dismutase(CuZn-SOD) activity in myocardium ,blood H2 O2 level were detected and the detection results were compared with those in the sham operation group .Results The rat ventricular remodeling in the myocardial infarction group (M group) was significant ,the left ventricular mass index (LVWI) was elevated ,the heart rate was increased and the hemodynamics was disordered(P<0 .05) .The SOD and CuZn-SOD expression in the myocardium and blood H2O2 expression were elevated(P<0 .05) .The LVW1 in different doses of simvastatin intervention groups were decreased compared with the myocardial infarction group(P<0 .05) ,the heart rate was decreased ,SOD and CuZn-SOD expression and blood H2 O2 expression were decreased ,the he-modynamics was improved(P<0 .05) ,especially which in the high dose atorvastatin intervention group (60 mg · kg -1 · d-1 ) were more significant .Conclusion Simvastatin reduces the expression of oxidative stress after acute myocardial infarction ,which may be one of the mechanisms for improving the ventricular remodeling and heart function ,and has certain positive correlation with dose .%目的：建立大鼠心肌梗死的模型，观察不同剂量辛伐他汀抑制心肌梗死后氧化应激的作用，探讨不同剂量辛伐他汀改善大鼠心室重塑和心功能的潜在机制。方法结扎大鼠冠状动脉前降支，形成急性心肌梗死模型，给予不同剂量辛伐他汀（20、40、60 mg · kg -1· d-1）干预。4周后，测定心脏心室重塑的各项指标，检测不同分组的大鼠心肌中总超氧化物歧化酶（SOD ）、铜锌-超氧化物歧化酶（CuZn-SOD）活性、血液H2 O2水平，并与假手术组比较。结果心肌梗死组大鼠心室重塑明显，左室心脏重量指数（LVWI）升高，心率增快，血流动力学紊乱（P＜0．05）。心肌中SOD、CuZn-SOD和血液中 H2O2水平升高（P＜0．05）。不同剂量辛伐他汀干预组均较心肌梗死组LVWI下降（P＜0．05），心肌中SOD、CuZn-SOD和血液中 H2 O2水平下降，心率减慢，血流动力学改善（P＜0．05），尤其以高剂量他汀干预组（60 mg · kg -1· d-1）更明显。结论辛伐他汀减少急性心肌梗死后氧化应激表达，可能是改善心室重塑和心功能的机制之一，并与剂量有一定的正相关性。