辛伐他汀对大鼠心肌肥厚的防治作用及其与钙通道的关系

目的 探讨辛伐他汀对心肌肥厚的防治作用及其与钙通道活动的关系.方法 采用腹主动脉缩窄术建立心肌肥厚动物模型.尾动脉无创测量大鼠收缩压.称量心脏重量/体重(HW/BW)、左心室重量/体重(LVW/BW)比值.采用超声心动图检测动物心脏构型及射血功能.应用RT-PCR和Western blot分别检测心肌L-型钙通道亚单位Cav1.2(α,C)、T-型钙通道亚单位Cav3.1 (α1G)、Cav3.2(α1H)mRNA及其蛋白表达的变化.结果 (1)腹主动脉缩窄+辛伐他汀组(AAC+SIM组)大鼠收缩压130 mm Hg(1 mm Hg=0.133 kPa)明显低于腹主动脉缩窄组(AAC组)189mm Hg,P<0.05.HW/BW比值AAC+SIM组3.37 mg/g明显低于AAC组3.94 mg/g,P<0.01.LVW/BW比值AAC+SIM组2.33 mg/g明显低于AAC组2.95 mg/g,P<0.01.室间隔厚度AAC+SIM组2.01 mm明显低于AAC组2.31 mm,P<0.01.左心室后壁厚度AAC+SIM组1.89 mm明显低于AAC组2.19 mm,P<0.01.(2)AAC+SIM组大鼠心肌T-型钙通道亚单位α1G、α1H mRNA和蛋白表达均显著低于AAC组,P均<0.01,但L-型钙通道亚单位α1 C mRNA和蛋白表达两组间比较差异无统计学意义.结论 辛伐他汀对腹主动脉缩窄所致的心肌肥厚具有明显的防治作用,其作用机制可能与其抑制T-型钙通道亚单位α1G、α1H mRNA和蛋白的重新再表达有关,但与L-型钙通道亚单位α1C mRNA和蛋白表达无关.

The effects of simvastatin on cardiac hypertrophy and association on calcium channel modulation in rats with myocardial hypertrophy induced by abdominal aortic constriction

Objective To investigate the effects of simvastatin(SIM)on cardiac hypertrophy and association with calcium channel modulation in rats with myocardial hypertrophy.Methods Myocardial hypertrophy was induced by abdominal aortic constriction(AAC)in adult SD rats.Following groups were studied(n=8 each):sham group,AAC group,AAC+verapamil group(10 mg·kg-1·d-3 per gavage for 4 weeks),AAC+SIM group(10 mg·kg-1·d-1 per gavage for 4 weeks)AAC+SIM+mevalonic acid (50 mg·kg-1·d-1 per gavage for 4 weeks)group.Systolic blood pressure(SBP),echocardiography,heart weight/body weight(HW/BW)and left ventricle weight/body weisht(LVW/BW)ratios were measured.The protein and mRNA expressions of L-type calcium channel subunit α1C and T-type calcium channel subunit α1 G and α1 H were detected by Western blot and RT-PCR respectively.Results SBP,HW/BW,LVW/BW,IVS and LVPW thickness,left ventricular weights were significantly increased in AAC rats and these effects could be significantly reduced by verapamil and SIM.The protein and mRNA expressions of α1G and α1H were significantly increased in AAC rats which could also be significantly inhibited by SIM or verapamil.The effects of SIM could be blocked by cotreatment with mevalonic acid.Protein and mRNA expressions of L-type calcium channel α1C were similar among groups.Conclusion Similar as verapamil,SIM could prevent AAC induced cardiac hypertrophy,possibly via inhibiting T-type calcium channel subunit α1 G and α1 H re-expression.