Fan Qian, Chen Mulei, Fang Xiangyang, Lau Wayne Bond, Xue Lei, Zhao Lina, Zhang Hui, Liang Yan-Hong, Bai Xi, Niu Hong-Yu, Ye Jing, Chen Qing, Yang Xinchun, Liu Miaobing
Department of Gerontology, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing, 100020, People's Republic of China.
Age (Dordr). 2013 Aug;35(4):1017-26. doi: 10.1007/s11357-012-9421-y. Epub 2012 May 12.
Previous studies indicate aging results in significantly decreased cardiac function and increased myocardial apoptosis after myocardial ischemia/reperfusion (MI/R) in humans or rats. The underlying mechanisms of aging-exacerbated effects remain unknown. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are known to play vital roles in aging-related MI/R injury. Heretofore, the effects of aging upon ROS and RNS formation were not investigated in humans, which is the focus of the current study. Due to experimental limitations with clinical trials, an additional animal experiment was performed. All enrolled acute myocardial infarction (AMI) patients received percutaneous coronary intervention (PCI) therapy. AMI patients were assigned into two groups: adult (age <65, n = 34) and elderly (age ≥65, n = 45) AMI patients. Blood samples were obtained from all study participants at 24 h and 3 days post-PCI. Plasma/white blood cell (WBC) ROS and RNS markers (malondialdehyde (MDA), myeloperoxidase (MPO), reduced glutathione (GSH), inducible nitric oxide synthase (iNOS) activity, NOx, and nitrotyrosine) were determined. The same markers were determined in rat cardiac tissue after 24 h MI/R. Compared to the adult group, elderly patients manifested increased plasma MDA and MPO and decreased plasma GSH concentrations. No significant differences in plasma NOx or nitrotyrosine concentration existed between adult and elderly patients. Furthermore, WBC iNOS activity in elderly patients was significantly decreased compared to the adult group. The measurement of ROS markers in the rat experiments was consistent and supported human study data. Surprisingly, RNS markers (NOx and nitrotyrosine) in blood and heart tissue increased from young to middle-aged rats but decreased from middle age to old age. Aging augments ROS, which might exacerbate MI/R injury. Additionally, our data support aging-induced changes of RNS levels in humans and rats in vivo.
先前的研究表明，在人类或大鼠中，衰老会导致心肌缺血/再灌注（MI/R）后心脏功能显著下降以及心肌细胞凋亡增加。衰老加剧这些影响的潜在机制尚不清楚。已知活性氧（ROS）和活性氮（RNS）在与衰老相关的MI/R损伤中起着至关重要的作用。迄今为止，尚未在人类中研究衰老对ROS和RNS形成的影响，这是本研究的重点。由于临床试验的实验局限性，还进行了一项动物实验。所有入选的急性心肌梗死（AMI）患者均接受经皮冠状动脉介入治疗（PCI）。AMI患者被分为两组：成年（年龄<65岁，n = 34）和老年（年龄≥65岁，n = 45）AMI患者。在PCI术后24小时和3天从所有研究参与者中采集血样。测定血浆/白细胞（WBC）ROS和RNS标志物（丙二醛（MDA）、髓过氧化物酶（MPO）、还原型谷胱甘肽（GSH）、诱导型一氧化氮合酶（iNOS）活性、NOx和硝基酪氨酸）。在大鼠心肌缺血/再灌注24小时后，测定心脏组织中的相同标志物。与成年组相比，老年患者的血浆MDA和MPO增加，血浆GSH浓度降低。成年和老年患者之间血浆NOx或硝基酪氨酸浓度无显著差异。此外，与成年组相比，老年患者的白细胞iNOS活性显著降低。大鼠实验中ROS标志物的测量结果与人类研究数据一致并支持该数据。令人惊讶的是，血液和心脏组织中的RNS标志物（NOx和硝基酪氨酸）从年轻大鼠到中年大鼠增加，但从中年到老年大鼠减少。衰老会增加ROS，这可能会加剧MI/R损伤。此外，我们的数据支持衰老在体内诱导人类和大鼠RNS水平的变化。
