不同剂量辛伐他汀对慢性心力衰竭兔左室重塑及心功能的影响

Effects of different doses of simvastatin on the left ventricle remodeling and heart functions in chronic heart failure rabbits

目的:通过观察不同剂量辛伐他汀对慢性心力衰竭(CHF)左室重塑及心功能的影响,探讨辛伐他汀对慢性心力衰竭兔心肌细胞发挥保护作用的机制。方法:雄性大耳白兔60只,随机分成5组,正常对照(CON)组,慢性心力衰竭(CHF)组,低剂量辛伐他汀(SD-SIM组),中剂量辛伐他汀(MD-SIM)组,高剂量辛伐他汀(HD-SIM)组。耳缘静脉注射阿霉素(ADR),制作CHF模型。行心脏彩超检查,测量左室结构、功能,测定血流动力学指标。处死动物后,留取左心室室壁多聚甲醛固定,染色后进行免疫组化检测热休克蛋白22(HSP22)表达水平。结果:心功能检查显示,与CON组相比SD-SIM、MD-SIM、HDSIM、CHF组左心室射血分数(LVEF)明显下降(P<0.05),与MD-SIM组相比,SD-SIM组、HD-SIM组明显下降(P<0.05);与CON组相比SD-SIM、MD-SIM、HD-SIM、CHF组左室舒张末内径(LVEDD)、左室收缩末内径(LVESD)显著增加(P<0.05),与MD-SIM组相比,SD-SIM组和HD-SIM组明显增大(P<0.05);血流动力学检测显示:与CON组相比,SD-SIM组、MD-SIM组、HD-SIM组、CHF组的+dp/dtmax、-dp/dtmax及LVSP明显下降(P<0.05),SD-SIM组、HD-SIM组与MD-SIM组相比明显下降(P<0.05)。HSP22的表达:与CON组相比SD-SIM组、MD-SIM组、HD-SIM组、CHF组HSP22蛋白的表达明显增多(P<0.01),SD-SIM组、MD-SIM组、HD-SIM组与CHF组相比表达明显减少(P<0.05),其中MD-SIM组表达最少(P<0.05)。结论:辛伐他汀可明显改善慢性心力衰竭兔左室重塑,改善心功能,其中MD-SIM组效果最好,其机制可能与辛伐他汀抑制HSP22的表达有关。

To explore the possible protective mechanism of different doses of simvastatin on the left ventricle remodeling and the cardiac functions in rabbits with adriamycin-induced heart failure. METHODS Sixty male rabbits were ran- domly divided into five groups （12 rabbits in each group） ：control group（CON） ,CHF group,small-dose simvastatin group （SD- SIM）, medium-dose simvastatin group（MD-SIM）, and high-dose simvastatin （HD-SIM）. Except for the control group, the mod- el of CHF was established by injecting adrinmycin（ADR） via the auricular vein of rabbits. Two weeks after adriamycin injec- tion,color Doppler ultrasonography were taken for measuring the left ventricular structure and the function, and the hemody- namic indexes. Left ventricular walls were taken for fixation with formaldehyde. Immunohistochemical staining was performed to detect the expressions of heat shock protein22 （HSP22）.