心力衰竭患者心肌线粒体DNA缺失突变的定量分析及与心功能损害程度的关系

Quantitative analysis of myocardial mitochondrial DNA deletion and its relationship with cardiac dysfunction in heart failure

目的为探讨心肌线粒体ＤＮＡ（ｍｔＤＮＡ）获得性损伤在衰竭心肌发病中的意义。方法对２８例慢性心力衰竭患者活检心肌，用定量ＰＣＲ方法，以常发缺失型突变ｍｔＤＮＡ４９７７ｂｐ（ｍｔ－ＤＮＡ４９７７）和７４３６ｂｐ（ｍｔＤＮＡ７４３６）缺失率为指标，观察心力衰竭不同发展阶段ｍｔＤＮＡ损伤程度与患者临床心功能受损之间的关系。结果慢性心力衰竭患者活检心肌中ｍｔＤＮＡ４９７７缺失频率为１００％，缺失率在０．１０３％～１．０２８％之间；７０％的扩张型心肌病（ＤＣＭ）和３８．９％的风湿性心脏病（ＲＨＤ）患者存在ｍｔＤＮＡ７４３６缺失，缺失率在０．００９％～０．４８８％之间。１０例健康对照者中，仅２例４５岁以上者有低水平的ｍｔＤＮＡ缺失。心功能愈差，左房扩大愈明显者，ｍｔＤＮＡ缺失率愈高；扩张型心肌病缺失程度明显高于风湿性心脏病。结论心肌ｍｔＤＮＡ损伤与心脏功能的受损程度密切相关，特别是ＤＣＭ患者。

Objective To assess the effects of acquired myocardial mitochondrial DNA (mtDNA) damage in the development of heart failure. Methods Twenty eight patients with congestive heart failure who underwent endomyocardial biopsy, together with 10 control hearts obtained at autopsy from people who died from accident were enrolled. The mtDNA deletions were analyzed by quantitative polymerase chain reaction(PCR) technique. The frequency and extent of two commonly encountered mtDNA deletions, mtDNA 4977 bp(mtDNA 4977 ) and 7436 bp(mtDNA 7436 ) deletions were used as the damage index to assess the relationship of the extent of mtDNA damage with the degree of cardiac dysfunction in the development of heart failure. Results mtDNA 4977 deletion was observed in the hearts of all of the patients with congestive heart failure, accounting for 0.103—1.028% of the total mtDNA; mtDNA 7436 deletion was found in 7 of 10 patients with dilated cardiomyopathy (DCM) and 7 of 18 patients with rheumatic heart disease (RHD), and comprised 0.009—0.488% of the total. Quantitatively very low mtDNA 4977 and mtDNA 7436 deletions were detected only in 2 and 2 control hearts respectively. With the rising of NYHA function class and the enlarged left atrial size, the percentage of mtDNA deletions increased markedly; and the extent of increase in DCM was more marked than that in RHD. Conclusion The extent of myocadial mtDNA damage varied closely with the degree of cardiac dysfunction, especially in patients with DCM.