AIM : To investigate the change and the mechanism of muscle ring finger 1( MuRF - 1 ) on heartfunctions and cardiac troponin Ⅰ( cTnI ) in myocardial infarction rats and to analyze the correlation hetween MuRF - 1 and cTnI.METHODS: The rats either with coronary artery ligation or with sham operation( 48 rats ) were divided into 4groups: sham( sham - operated ) group, MI( myocardial infarc:tion ) group , MG - 132( N - [ ( phenylmethoxy )carbonyl ] L - leucyl - N -[ ( 15 ) - 1 - formyl - 3 - methylhutyl ] - L - leucinamide ) group and TNF - α( tumor necrosis factor alpha ) 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 - hrain natriuretic peptide( NT - proBNP ) and cardio - pathologic changes were observed.Both mRNA and protein expressions of MuRF - 1 and cTnl in the left ventricles were determined hy 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 animals had a decreasing tendency in MG - 132 group, and NT - proBNP level as well as the left ventricular end - diastolic pressure( LVEDP ) were significantly dec:reased( 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 cTnl 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 protein levels.In contrast, treatment with TNF - α worsened the heart failure , reduced the cTnl level and raised MuRF - 1 level.The expression of MuRF - 1 at mRNA and protein levels had significantly negative correlation with the expression of cTnI in all groups.CONCLUSION: These data suggest that MuRF - 1 is significantly increased in chronic heart failure and aggravates heart dysfunction hy depressing cTnI level.Inhibition of proteasome activity diminishes MuRF - 1 expression.MuRF - 1 may be involved in the mechanism of chronic heart failure.%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.
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