心力衰竭患者心肌线粒体脱氧核糖核酸损伤与衰竭心肌线粒体酶活性的关系

The Effects of Myocardial Mitochondrial DNA Damage on Myocardial Mitochondrial Respiratory Chain Enzyme Activities in Patients with Heart Failure

目的 :为探讨心肌线粒体脱氧核糖核酸 (mt DNA)获得性损伤对衰竭心肌线粒体酶活性改变的影响 ,确立 mt DNA损伤在衰竭心肌发病中的作用。 方法 :对 2 8例慢性心力衰竭患者活检心肌 ,用定量聚合酶链式反应 (PCR)及生化方法 ,观察衰竭心肌中常发缺失型突变 mt DNA4977和 mt DNA7436 缺失率与线粒体呼吸酶活性和心脏功能受损之间的关系。 结果 :慢性心力衰竭患者活检心肌中的 mt DNA存在不同程度的缺失突变损伤 ,两种缺失类型合计的缺失率在0 .10 2 %～ 1.745 %之间 ;mt DNA缺失率与心肌生化水平上的线粒体呼吸酶活性改变相关性良好 ;同时与整体水平上的心脏泵功能受损呈一致性关系。 结论 :心肌 mt DNA损伤与心肌线粒体呼吸功能下降和心脏功能受损程度密切相关 ,提示 mt DNA损伤可能参与了心力衰竭的形成与发展。

Objective:To assess the effects of acquired myocardial mitochondrial DNA (mtDNA) damage on myocardial mitochondrial respiratory chain enzyme activities in the development of heart failure. Methods:The relationship between the frequency and extent of two commonly encountered mtDNA,mtDNA4977(mtDNA 4977 ),7436(mtDNA 7436 ) deletions determined by quantitative polymerase chain reaction(PCR) technique and myocardial mitochondrial respiratory enzyme activities by biochemical assay,and cardiac function was analysed in 28 patients with congestive heart failure undergone endomyocardial biopsy. Results:Myocardial mtDNA of all 28 patients with CHF had deletions with different extents.The pooled mtDNA 4977 and mtDNA 7436 deletions comprised 0 102%～1 745% of the total mtDNA.The proportion of mtDNA 4977 ,mtDNA 7436 were negatively correlated with the mitochondrial respiratory chain enzyme activities.With the increasing of the percentages of mtDNA deletions,the cardiac ejection fraction was decreased significantly. Conclusion:There was good correlation between the proportion of mtDNA deletions and mitochondrial respiratory chain enzyme activities as well as cardiac dysfunction.The mtDNA deletions may be an important contributory factor to the development of heart failure.