辛伐他汀抑制大鼠急性心肌梗死后血管紧张素Ⅱ的生成和改善心室重塑的研究

Study of abating angiotensin II and improving cardiac remodeling by simvastatin after acute myocardiac infarction in rats

目的 在大鼠结扎前降支致心肌梗死的模型上观察辛伐他汀抑制血管紧张素Ⅱ (AngⅡ )及AngⅡ诱导的活性氧(H2 O2 )生成 ,是否有利于改善心室重塑和心功能的作用。方法 结扎大鼠冠状动脉前降支造成心肌梗死模型 ,给予辛伐他汀干预。 8周后 ,测定心脏重量指数、血流动力学指标、血液及心肌中AngⅡ含量 ,血液过氧化氢 (H2 O2 )含量 ,并与假手术组比较。结果 心肌梗死组 (M组 )大鼠右室重量指数 (RVWI)、左室重量指数 (LVWI)升高 (P <0 .0 1) ,外周动脉压 (APS)、舒张压 (APD)均降低 ,(P <0 .0 1)。左室收缩压 (LVSP)和心室收缩期室内压上升速率 (+dp/dtmax) ,心室舒张期室内压下降速率 (-dp/dtmax)下降(P <0 .0 1) ,左室舒张末压 (LVEDP)升高 (P <0 .0 1)。心肌、血液中AngⅡ含量升高 (P <0 .0 1) ;H2 O2 含量升高 (P <0 .0 1)。辛伐他汀干预组较M组辛RVWI、LVWI下降 (P <0 .0 1) ,APS、APD、LVSP、+dp/dtmax、-dp/dtma均回升 (P <0 .0 1) ,LVEDP回落(P <0 .0 1) ;心肌、血液中AngⅡ含量下降 (P <0 .0 1) ,H2 O2 含量下降 (P <0 .0 1)。结论 辛伐他汀抑制急性心肌梗死后血管紧张素Ⅱ (AngⅡ )及AngⅡ诱导的H2 O2 生成 ,可能是改善心室重塑和心功能的机制之一。

Objective To investigate the effects of simvastatin abating angiotensin Ⅱ(AngⅡ),H 2O 2 and improve cardiac remodeling and cardiac disfunction after myocardiac infarction in rats. Methods Simvastatin was given to the rats with myocardiac infarction by left anterior decending coronary artery ligation. After 8 weeks, cardiac remodeling was observed through right ventricular weight index (RVWI),left ventricular weight index (LVWI),changes of hemodynamics were observed. The activity of AngⅡin left ventricular in serum and hydrogen peroxide (H 2O 2) in serum were measured.Results Compared with controls, the rat model of myocardiac infarction induced RVWI, LVWI increase; left ventricular systolic pressure (LVSP),the ventricular pressure rise ratio during systolic period(+dp/dt max ),the ventricular pressure rise decay ratio during diastolic period (-dp/dt max ) decline (each P<0.01) and left ventricular end diastolic pressure (LVEDP) rise (P<0.01). Simvastatin attenuated RVWI, LVWI (each P<0.01) and decreased content of AngⅡ,H 2O 2 in serum (each P<0.01).APS APD LVSP +dp/dt max ,-dp/dt max (P<0.01) rised while LVEDP decreased(each P<0.01).Conclusion Simvastatin abates angiotensin Ⅱ,H 2O 2 and improves cardiac remodeling and cardiac disfunction after acute myocardiac infarction.