外周血白细胞端粒长度和线粒体基因拷贝数对急性心肌梗死的诊断预测价值以及相关机制的探讨

The predictive value of telomere length and mitochondrial DNA copy number of peripheral blood leukocytes for acute myocardial infarction and related mechanism

目的探究外周血白细胞端粒长度(LTL)和线粒体基因拷贝数(mtDNA-CN)对急性心肌梗死(AMI)的预测价值,并从端粒酶逆转录酶(TERT)和线粒体氧化损伤的角度探讨其相关机制。方法选取AMI患者80例,并选同期行冠脉造影检查且结果显示冠脉大致正常者80例作为对照。收集研究对象的临床资料和空腹全血,以qPCR法检测外周血LTL、TERT mRNA、mtDNA-CN和线粒体氧化损伤程度,采用Spearman相关分析评估上述指标间的相关性。采用多因素Logistic回归分析LTL和mtDNA-CN与AMI发生风险的关系,以受试者工作曲线(ROC)评价LTL和mtDNA-CN对AMI诊断的预测价值。结果 AMI组患者外周血LTL、TERT mRNA表达水平和mtDNA-CN均显著低于对照组,线粒体氧化损伤水平显著高于对照组,差异均具有统计学意义(P<0.05)。在AMI组和对照组中,LTL分别与TERT mRNA的表达水平和mtDNA-CN呈显著正相关,与线粒体氧化损伤水平呈显著负相关(均P<0.05)。在AMI组中,mtDNA-CN与线粒体氧化损伤水平呈显著负相关(P=0.03),但在对照组中两者相关性无统计学意义(P=0.20)。Logistic回归分析结果表明,长LTL和高mtDNA-CN是AMI的保护因素;ROC曲线分析结果表明,LTL、mtDNA-CN以及两者联合预测AMI的曲线下面积(AUC)分别为0.748、0.704、0.767。结论外周血LTL和mtDNA-CN对AMI具有一定的预测诊断价值。AMI患者外周血LTL的缩短可能与TERT mRNA表达的降低有关,外周血白细胞线粒体氧化损伤水平的升高可能是mtDNA-CN降低和LTL缩短的重要原因。

Objective To investigate the predictive value of peripheral blood leukocyte telomere length(LTL) and mitochondrial DNA copy number(mtDNA-CN) for acute myocardial infarction(AMI),and to explore the regulatory role of telomerase reverse transcriptase(TERT) mRNA expression and mitochondrial oxidative damage.Methods Eighty patients with AMI were selected while another 80 patients whose coronary angiography results proved them to be generally healthy were selected as the control group.LTL,TERT mRNA,mtDNA-CN and the level of mitochondria oxidative damage in peripheral blood were determined by quantitative real-time PCR(qPCR).The correlations between the above indicators were determined by spearman correlation analysis.A multiple Logistic regression was performed to analyze the correlations of LTL and mtDNA-CN with the risk of AMI.Finally,the predictive value of LTL and mtDNA-CN for AMI was assessed by receiver operating characteristic(ROC) curves.Results LTL,TERT mRNA and mtDNA-CN in peripheral blood were significantly lower while the level of mitochondrial oxidative damage was significantly elevated in the AMI group than in the control group.In the AMI and the control groups,LTL was positively correlated with TERT mRNA expression levels and mtDNA-CN,respectively,but negatively correlated with the level of mitochondrial oxidative damage(all P<0.05).MtDNA-CN was negatively correlated with the level of mitochondrial oxidative damage in the AMI group(P=0.03),but not in the control group(P=0.20).Multivariable Logistic regression analysis showed that longer LTL and higher mtDNA-CN were protective factors for AMI.The ROC curve analysis showed that the area under the curve(AUC) of LTL,mtDNA-CN and the combination of both was 0.748,0.704 and 0.767,respectively.Conclusion Peripheral blood LTL and mtDNA-CN are of predictive value for AMI. The shortened LTL in peripheral blood of AMI patients may be related to lower TERT mRNA expressions.In addition,the increase in mitochondrial oxidative damage in peripheral blood leukocytes may be one of the important mechanisms by which mtDNA-CN is decreased and LTL is shortened.