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摘要: 目的:观察不同时期辛伐他汀对兔慢性心力衰竭 (CHF) 心肌重构的影响, 探讨辛伐他汀对CHF心肌细胞的保护作用机制。方法:新西兰大白兔48只, 随机分为对照组、CHF组、早期辛伐他汀组 (E-SIM) 和晚期辛伐他汀组 (L-SIM)。除对照组外, 其余3组按2ml/kg体重经耳缘静脉注射1mg/ml阿霉素0.9%氯化钠溶液, 每周1次, 连续10周;对照组用相同容量的0.9%氯化钠经耳缘静脉注射。E-SIM组在首次注射阿霉素时给予1.5mg·kg-1·d-1的辛伐他汀灌胃, L-SIM组于第3周时开始给予相同剂量的辛伐他汀灌胃, 一直持续到第12周;CHF组和对照组则给予相同容积的0.9%氯化钠灌胃。第12周结束时行心脏彩超检查;取左心室进行HE染色、Masson染色, 用RT-PCR监测过氧化物酶增殖体激活型受体γ (PPARγ) mRNA表达水平。结果:大体标本显示, 与对照组相比, 其他3组左室壁变薄, 心室腔扩大, 但E-SIM组及L-SIM组较CHF组扩大程度小。与对照组相比, 其余各组左心室射血分数 (LVEF) 明显下降 (P<0.01), L-SIM组较E-SIM组降低明显 (P<0.05)。HE染色显示:CHF组心肌细胞大小不一、数量减少, 呈片状坏死, 纤维组织增生明显。E-SIM组和L-SIM组上述表现较轻, E-SIM组较L-SIM组心肌细胞排列整齐, 纤维组织增生较少。与对照组比较, 其他3组PPARγmRNA表达均降低 (均P<0.01), E-SIM组和L-SIM组较CHF组表达增加 (P<0.01), E-SIM组较L-SIM组明显增加 (P<0.05)。结论:辛伐他汀能抑制CHF兔的心肌重构, 改善心脏功能, 早期应用效果较明显。Abstract: Objective:To investigate the effect of myocardial remodeling on rabbit with adriamycin-induced chronic heart failure (CHF) and explore the mechanism.Method:Fourty-eight male rabbits were randomly divided into four groups:control group, chronic heart failure group (CHF group), early-simvatatin treatment group (E-SIM group) and later-simvatatin group (L-SIM group).The control group received peritoneal injection with normal sodium once a week for ten weeks.Adriamycin was given to the other groups with the dosage of 2 ml/kg diluted to 1 mg/ml with normal sodium once a week, all for ten times.At the meantime the E-SIM group received simvastatin 1.5 mg·kg-1·d-1 for twelve weeks.After two weeks, the L-SIM group received the same dose simvastatin for ten weeks.In the course of experiment, observing the general state of the rabbits regularly such as the mental state, action, collar pattern, food intake, weight and ascite.Twelve weeks latter, all rabbit were sactificed after hemodynamics surveyed and performed echocardiography.Morphological characteristics were measured with HE staining and Masson staining.Result:Compared to control group, left ventricle enlarged and left ventricular ejection fraction dropped in the CHF group, E-SIM group and L-SIM group (P<0.01).Compared with CHF group, the condition of ventricle function was better in E-SIM group and L-SIM group (P<0.05), and E-SIM group was better than L-SIM group (P<0.05).HE straining displayed cardiac muscle cells had different dimention, decreased numbers, lamellar necrosis, significant hyperplasia of microstructure in CHF group, E-SIM group and L-SIM group were better than control group, E-SIM group was better than L-SIM group. Compared with control group, the expressions of PPARγ mRNA were decreased obviously in E-SIM group, L-SIM group and CHF group, while increased significantly in L-SIM group and E-SIM group compared with CHF group, the increase in E-SIM group was more obviously (all P<0.05).Conclusion:Simvastatin can inhibit cardiac remodeling and improve chronic heart failure, and early application makes effect obvious.
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Key words:
- chronic heart failure /
- adriamycin /
- cardiac remodeling /
- simvastatin /
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