MuRF-1在大鼠心肌梗死后慢性心衰心脏中的表达变化及其分子机制的探讨被引量：1

Transformation of muscle ring finger 1 on chronic heart failure in myocardial infarction rats

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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。 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 the heart failure, reduced the cTnI level and raised MuRF - 1 level. The expression of MuRF - 1 at mRNA and protein levels had significantly negative correlation with the ex- pression of cTnI in all groups. CONCLUSION： These data suggest tha~ MuRF - 1 is significantly irtereased in chronic heart failure and aggravates heart dysfunction by depressing cTnI level. Inhibition of proteasome activity diminishes MuRF - 1 expression. MuRF - 1 may be involved in the mechanism of chronic heart failure.

作者戴翠莲张赟姜黔峰

机构地区合肥医学院附属医院心内科

出处《中国病理生理杂志》 CAS CSCD 北大核心 2011年第2期215-222,共8页 Chinese Journal of Pathophysiology

基金国家自然科学基金资助项目(No.30860295)

关键词心力衰竭肌肉环指蛋白-1 肌钙蛋白Ⅰ Heart failure Muscle ring finger 1 Troponin I

分类号 R541.05 [医药卫生—心血管疾病]

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参考文献18

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