扩张型心肌病患者心肌线粒体DNA缺失突变及与心衰发病的关系

为探讨扩张型心肌病（DCM）患者心肌线粒体DNA（mtDNA）缺失突变对心衰发病的意义，10例DCM患者心内膜活检心肌，用定量PCR方法，以常发缺失型突变mtDNA4977bp（mtDNA4977）和7436bp（mtDNA7436）缺失率为损伤指标，观察心衰不同发展阶段mtDNA缺失程度与患者心肌线粒体呼吸酶活性改变及临床心功能受损之间的关系。结果表明：DCM患者活检心肌中mtDNA4977缺失频率为100％，缺失率在0．128％～1．028％之间；mtDNA7436的缺失频率为70％，缺失率为0．103％～0．843％；10例健康对照中，仅2例45岁以上者有低水平的mtDNA4977及mtDNA7436缺失。心功能愈差，心脏扩大愈显著者，mtDNA缺失率愈高，心肌线粒体呼吸酶活性降低程度也愈明显；mtDNA缺失程度与心肌线粒体呼吸酶活性改变及整体心功能受损之间有着良好的一致性关系。提示mtDNA缺失可能参与了DCM心衰的形成与发展过程。

MYOCARDIAL MITOCHONDRIAL DNA DELETIONS AND THEIR CONTRIBUTORY EFFECT TO CARDIAC DYSFUNCTION IN THE PATIENTS WITH DILATED CARDIOMYOPATHY

Aim: To assess the effects of myocardial mitochondrial DNA (mtDNA) deletions onthe development of heart failure in patients with idiopathic dilated cardiomyopathy (DCM). Methods:10 patients with DCM who underwent endomyocardial biopsy,together with 10 control hearts obtainedat autopsy from people who died from accident wereenrolled. The mtDNA deletions were analyzed byquantitative polymerase chain reaction (PCR) technique. The frequency and extent of two commonlyencountered mtDNA deletions, mtDNA 4977bp(mtDNA4977 ) and 7436hp (mtDNA7436 ) deletionswere used as the damage index to assess the relationship of the extent of mtDNA damage with thedegree of cardiac dysfunction in the development ofheart failure. Results: mtDNA4977 deletion was observed in the hearts of all of the patients with DCM.accounting for 0. 128% ~ 1. 028% of the total mtDNA; mtDN7436 deletion was found in 7 of 10 patients with DCM,and comprised 0. 103 % ~ 0. 843 %of the total. MtDNA4977 and mtDNA7436 deletionswere detected only in 2 control hearts respectively.and with very low quantitatively. In patients withdifferent heart function condition,the extent of mtDNA deletions was diverse. With the rising NYHAfunction stages and the enlarged cardiac size. theproportion of mtDNA deletions incresed markedly;and the myocardial mitochodrial respiratory chainenzyme activities were also reduced significantly,There wre well correlation among the extent of myocardial mtDNA damage.the reduction of my-ocardial