目的观察辛伐他汀对兔慢性心力衰竭模型心肌肥厚、心功能的影响,探讨辛伐他汀抑制心肌肥厚、改善心功能的机制。方法24只新西兰白兔分为4组,1组为假手术组。2、3、4组给予主动脉瓣返流及腹主动脉缩窄术,其中2组为心衰对照组;3组:早干预组,术后给予辛伐他汀5mg·kg-1·d-1灌胃连续8wk;4组:晚干预组,术后4wk给予辛伐他汀5mg·kg-1·d-1灌胃连续4wk。观察开始及结束时左室舒张末压(LVEDP)。实验结束时,观察左心室重量(LVW)、心脏重量(HW),计算左心室重量指数(LVW/BW)、心脏重量指数(HW/BW)。RT-PCR分析各组PPARγmRNA表达。Western blot分析心肌细胞核PPARγ和p65蛋白表达,电泳迁移率变动试验分析p65活性。结果早、晚干预组LVW、HW、HW/BW均低于心衰对照组(P<0.05,P<0.01),早干预组(LVW/BW)低于心衰对照组(P<0.01)。早、晚干预组左室舒张末压低于心力衰竭组(P<0.01)。心衰对照组心肌组织PPARγ蛋白和mRNA表达低于假手术组(P<0.01),p65蛋白表达及活性高于假手术组(P<0.01)。辛伐他汀干预后,早干预组、晚干预组PPARγ蛋白和mRNA表达增加(P<0.01),p65蛋白表达及活性降低(P<0.01)。结论辛伐他汀抑制心肌肥厚、改善心功能,其机制与增加PPARγ表达、降低p65蛋白表达及活性有关。 Objective To observe the effects of simvastatin on cardiac hypertrophy and cardiac function in a rabbit model of chronic heart failure and to investigate the mechanism of simvastatin inhibiting cardiac hypertrophy and improving cardiac function. Methods Twenty-four New Zealand white rabbits were divided into 4 groups, one group was sham operation group. Groups 3, 4 were given aortic valve regurgitation and abdominal aortic constriction, of which 2 were heart failure control group; 3 groups: early intervention group, postoperative simvastatin 5 mg · kg -1 · d- 1 for 8 weeks continuously. Group 4: late intervention group, simvastatin 5 mg · kg-1 · d-1 for 4 weeks after 4 weeks. Left ventricular end-diastolic pressure (LVEDP) was observed at the beginning and at the end. At the end of the experiment, left ventricular mass (LVW), heart weight (HW), left ventricular mass index (LVW / BW) and heart weight index (HW / BW) were calculated. RT-PCR analysis of PPARγmRNA expression in each group. Western blot analysis of myocardial nuclear PPARγ and p65 protein expression, electrophoretic mobility shift assay analysis of p65 activity. Results The levels of LVW, HW and HW / BW in the intervention group were lower than those in the control group (P <0.05, P <0.01), and those in the early intervention group (LVW / BW) were lower than those in the control group (P <0.01). Left and right ventricular end-diastolic pressure in early intervention group and late intervention group were lower than those in heart failure group (P <0.01). The expression of PPARγ protein and mRNA in heart failure control group was lower than that in sham operation group (P <0.01). The expression and activity of p65 protein in myocardium of control group was higher than that of sham operation group (P <0.01). After simvastatin intervention, the expression of PPARγprotein and mRNA in early intervention group and late intervention group were increased (P <0.01), p65 protein expression and activity were decreased (P <0.01). Conclusion Simvastatin can inhibit cardiac hypertrophy and improve cardiac function. Its mechanism is related to increasing PPARγ expression and decreasing p65 protein expression and activity.