中文摘要：

目的：研究肌肉环指蛋白1（MuRF-1）在心肌梗（MI）死后慢性心衰大鼠心脏中的表达变化及其分子机制,对心功能及心肌肌钙蛋白I（cTnI）的影响及其与cTnI的关系.方法：将48只制作成功的心肌梗死大鼠及假手术大鼠纳入研究,分为sham组、MI组、MG-132组及TNF-α组,检测各样本血流动力学指标及血清N末端原脑钠肽水平（NT-proBNP）,观察心肌组织学变化;原位杂交及real-time PCR法半定量测定心肌组织MuRF-1及cTnI mRNA表达,Western blotting法确定心肌MuRF-1及cTnI蛋白质水平,并对MuRF-1及cTnI的相关性进行分析.结果：与MI及TNF-α组相比,MG-132能够显著降低NT-proBNP（P＜0.05）,使心衰的发生率及死亡率有下降趋势,心肌组织损伤减轻,并使大鼠左心室收缩压（LVSP）升高（P＜0.01）,左心室等容收缩期室内压最大上升速率（＋dp/dtmax）增加（P＜0.01）,左心室舒张末压（LVEDP）明显降低（P＜0.01）.与sham组相比,MI组MuRF-1的mRNA及蛋白质表达均显著升高（P＜0.05）,cTnI水平降低（P＜0.05）; MG-132能够明显降低心肌梗死后MuRF-1表达（P＜0.05）,升高cTnI水平（P＜0.01）;TNF-α则起相反作用.相关性分析显示,MuRF-1与cTnI呈显著负相关（P＜0.01）.结论：MuRF-1在慢性心衰中表达显著升高,使心功能损害加重,其作用通过抑制cTnI表达而实现;抑制蛋白酶体活性能够通过抑制MuRF-1表达而升高cTnI水平,改善心功能.MuRF-1的激活可能是慢性心力衰竭的机制之一.

英文摘要：

AIM： To investigate the change and the mechanism of muscle ring finger 1 （ MuRF - 1 ） on heart functions and cardiac troponin I（cTnI） in myocardial infarction rats and to analyze the correlation between MuRF- 1 and cTnI. METHODS： The rats either with coronary artery ligation or with sham operation （48 rats） were divided into 4 groups ： sham （ sham - operated） group, MI （ myocardial infarction） group, MG - 132 （ N - [ （phenylmethoxy） carbenyl ] - L - leucyl - N - [ （1S） - 1 - formyl - 3 - methylbutyl ] - L - leucinamide ） group and TNF - et （ tumor necrosis factor al- pha） group. The animals were treated with saline（ sham and MI group）, MG - 132（ MG - 132 group） or TNF - α（ TNF - α group） by intraperitoneal injection. Hemodynamics, N -terminal pro -brain natriuretic peptide（ NT -proBNP） and cardio - pathologic changes were observed. Both mRNA and protein expressions of MuRF - 1 and cTnI in the left ventricles were determined by real - time PCR and in situ hybridization or by Western blotting. The correlation between MuRF - 1 and cTnI was also analyzed. RESULTS ： Compared with MI group and TNF - α group, the mortality and the morbidity of the ani- mals had a decreasing tendency in MG- 132 group, and NT- proBNP level as well as the left ventricular end -diastolic pressure（LVEDP） were significantly decreased（ P 〈 0. 05 and P 〈 0. 01, respectively）. Left ventricular systolic pressure （LVSP） and the maximum rate of left ventricular pressure rise（ ＋ dp/dtmax） were pronouncedly increased（ P 〈 0. 01 ）. The heart injury was also amended after MG - 132 treatment. Compared with sham group, the mRNA and protein relative expressions of MuRF- 1 were predominantly increased in MI group （P 〈 0. 05 ）, and the eTnI levels were decreased （P〈0. 05）. MG - 132 depressed the level of MuRF- 1 （P 〈0. 05） and enhanced the level of cTnI（P 〈0. 01 ） at both mRNA and pro.tein levels. In contrast, treatment with TNF - α worsened