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目的探讨辛伐他汀对心力衰竭模型兔抑制心肌肥厚、改善心功能的影响及机制。方法24只新西兰白兔,均分四组,除假手术组外,通过破坏主动脉瓣和缩窄腹主动脉,增加左心室前、后负荷,建立慢性心力衰竭模型;术后(除心衰对照组)早干预组(即起,连续8周)和晚干预组(第5周起,连续4周)予辛伐他汀每天5mg/kg灌胃,实验结束取心肌细胞,Western-blot检测细胞膜RhoA蛋白表达,[γ-32P]电泳分析RhoGTPase活性;实验前、结束时均行超声心动图检查。结果心衰对照组室间隔厚度(LVSd)、左心室舒张期内径(LVIDd)、左心室后壁厚度(LVPwd)、左心室收缩期内径(LVIDs)、心脏重量(HW)、左心室重量(LVW)、心脏/体重(HW/BWradio)、左心室/体重(LVW/BWradio)明显高于假手术和早、晚干预组(P<0.05,P<0.01);左室射血分数(EF)、左室长轴缩短率(FS)明显低于假手术组和早、晚干预组(P<0.05,P<0.01);心肌细胞膜RhoA蛋白表达、RhoGTPase活性明显高于假手术组和早、晚干预组(P<0.01)。结论辛伐他汀可抑制细胞膜RhoA蛋白表达、RhoGTPase活性,从而抑制心肌肥厚、改善心功能。
Objective To investigate the effect and mechanism of simvastatin on cardiac hypertrophy and cardiac function in a model of heart failure. Methods Twenty-four New Zealand white rabbits were divided into four groups. Except for the sham-operation group, chronic heart failure model was established by destroying the aortic valve and narrowing the abdominal aorta and increasing the left ventricular anterior and posterior load. After operation, Control group) were given intraperitoneal injection of simvastatin 5 mg / kg orally in the early intervention group (ie, continuous for 8 weeks) and late intervention group (continuous for 4 weeks in the fifth week). Cardiomyocytes were harvested at the end of the experiment, RhoA protein expression, [γ-32P] electrophoresis analysis of RhoGTPase activity; before the experiment, at the end of echocardiography. Results LVSd, LVIDd, LVPwd, LVIDs, HW, LVW in the control group were significantly higher than those in the control group (HW / BWradio) and LVW / BWradio were significantly higher than those in sham operation and early and late intervention groups (P <0.05, P <0.01) The shortening rate of left ventricular long axis (FS) was significantly lower than that of the sham operation group and the early and late intervention groups (P <0.05, P <0.01). The RhoGTPase activity and RhoGTPase activity of the myocardial cell membrane were significantly higher than those of the sham operation group and the early and late intervention Group (P <0.01). Conclusion Simvastatin can inhibit RhoA protein expression and RhoGTPase activity in the cell membrane, thereby inhibiting cardiac hypertrophy and improving cardiac function.