线粒体应激蛋白沉默信息调节因子2相关酶3通过缺氧诱导因子-1α和核转录因子-κB信号通路保护心肌缺血损伤

Mitochondrial Stress Protein SIRT3 Prevents Myocardial Ischemia Through HIF-1α and NF-κB Signalings

目的 探讨心肌缺血患者外周血单个核细胞中沉默信息调节因子2相关酶3（SIRT3）、缺氧诱导因子-1α（HIF-1α）、核转录因子-κB（NF-κB）及其下游因子肿瘤坏死因子-α（TNF-α）的表达.方法 提取24名正常人（NC组）以及32例急性心肌梗死患者（AMI组）和21例陈旧性心肌梗死患者（OMI组）的外周血中单个核细胞（PBMCs）,用荧光实时定量多聚酶链反应（qPCR）检测PBMCs中SIRT3、HIF-1α、NF-κB、TNF-α的相对mRNA水平,并收集相关临床数据.结果 NC组、AMI组、OMI组的年龄,血压差异无统计学意义（P〉0.05）,qPCR结果显示AMI组患者PBMCs中的SIRT3、HIF-1α、NF-κB的mRNA含量均比NC组和OMI组高,差异有统计学意义（P〈0.05）;OMI组患者PBMCs中的SIRT3、HIF-1α的mRNA含量比NC组低,差异有统计学意义（P〈0.05）.AMI组患者PBMCs中的TNF-αmRNA含量比OMI组高,差异有统计学意义（P〈0.05）.相关性分析显示SIRT3 mRNA与TC（r=-0.355,P〈0.01）、LDL-C（r=-0.401,P〈0.01）存在显著性负相关关系,TNF-αmRNA与TC（r=-0.231,P〈0.05）存在显著性负相关关系,与LDL-C（r=0.276,P〈0.05）存在显著性正相关关系.结论 AMI组患者的SIRT3、HIF-1α、NF-κB、TNF-α的相对mRNA水平明显增高,而OMI组患者的SIRT3的相对mRNA水平较NC组低,提示线粒体应激蛋白SIRT3可能通过HIF-1α和NF-κB信号通路保护心肌缺血损伤;进一步研究发现SIRT3 mRNA与TC、LDL-C呈负相关,推测SIRT3可能参与血脂的调节作用影响冠状动脉粥样硬化的形成与发展.

Objective To explore the expression of SIRT3, HIF-1α, NF-κB and TNF-αin peripheral blood mononuclear cell （PBMCs） of patient with myocardial ischemia.Methods Peripheral blood and biochemical data were collected from 24 healthy individuals （normal control group, NC group） and 32 cases of patients with acute myocardial infarction （acute myocardial infarction group, AMI group） and 21 old myocardial infarction patients （old myocardial infarction group, OMI group）. The levels of SIRT3, HIF-1α, NF-κB, TNF-α mRNA in PBMCs was assayed by Real-time Quantitative polymerase chain reaction （qPCR）.Results The ages and blood pressure had no difference in all three groups. The level of SIRT3, HIF-1α, NF-κB mRNA in AMI group were higher than those in NC group and OMI group （P〈0.05）, SIRT3 and HIF-1α mRNA levels in OMI group were lower than those in NC group （P〈0.05）, TNF-α mRNA levels in AMI group were higher than it in OMI group （P〈0.05）. Correlation analysis showed that there is a negative correlation between SIRT3 mRNA levels with TC （r=-0.355,P〈0.01） and LDL-C （r=-0.401,P〈0.01）, a negative correlation between TNF-α mRNA levels with TC （r=-0.231,P〈0.05）, a positive correlation between TNF-α mRNA levels with LDL-C （r=0.276,P〈0.05）. Conclusion Our present study indicates SIRT3, HIF-1α, NF-κB and TNF-α were related to myocardial ischemia injury and play an important role in the development of AMI diseases. Mitochondrial stress protein SIRT3 prevents myocardial ischemia through HIF-1α and NF-κB signalings.