Objective To explore the influence of aging on levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in patients and rats with acute myocardial infarction (AMI) by clinical research and animal experiments.Methods Totally 104 patients with AMI who underwent percutaneous coronary intervention (PCI) from September 2013 to March 2015 were selected,37 adult patients were finally enrolled and divided into adult group (＜65 years old,37 cases) and elderly group (≥65 years old,49 cases).The plasma levels of ROS [malondialdehyde (MDA),myeloperoxidase (MPO) and glutathione (GSH)] and RNS [inducible nitric oxide synthase (iNOS) activity,NOx and nitrotyrosine (ONOO-)] 24 h and 3 d after PCI were compared between groups.Because of the limitation of clinical research,a corresponding animal experiment was designed.Totally 72 Sprague Dawley rats were randomly divided into 6 groups (young rats 2 months old,middle-aged rats 10 months old,elderly rats 24 months):young control group,middle-aged control group,elderly control group,young ischemia/reperfusion (L/R) group,middle-aged I/R group,elderly I/R group (12 rats in each group).Myocardial I/R was established by ligation of left coronary artery for 30 min,followed by reperfusion for 24 h in I/R group,while not in control group.The myocardial tissue and blood samples were collected to detect the levels of ROS [MDA,MPO and GSH] and RNS [iNOS activity,NOx and ONOO-] and then compared among groups.Results The plasma levels of MDA and MPO were significantly higher,the level of GSH was significantly lower in elderly group than those in adult group 24 h and 3 d after PCI [MDA:(8.6 ±2.3) μmol/L vs (4.8 ± 1.0) μmol/L,(7.5 ± 1.8) μmol/L vs (3.5 ±0.8) μmol/L;MPO:(707 ±224) μg/L vs (474 ± 126) μg/L,(667 ± 187) μg/L vs (377 ± 114) μg/L;GSH:(2.6 ± 1.1) μmol/L vs(3.7 ± 1.0) μmol/L,(1.7 ± 0.9) μmol/L vs (2.5 ± 1.1) μmol/L] (P ＜0.01).The activity of iNOS was significantly decreased in elderly group compared with adult group [(28 ± 11) pmol/mg protein · min vs (34 ± 9) pmol/mg protein · min,(20 ± 8) pmol/mg protein · min vs (24 ± 8) pmol/mg protein · min] (P ＜0.01).The rat experiment data were consistent and supported human study data.Conclusion Aging augments ROS and RNS in humans and rats in vivo,which exacerbates myocardium I/R injury.%目的 通过临床研究和相应的动物实验探讨衰老对急性心肌梗死(AMI)患者及大鼠体内活性氧介质(ROS)和活性氮介质(RNS)水平的影响.方法 选取2013年9月至2015年3月首都医科大学附属北京安贞医院接受经皮冠状动脉介入治疗(PCI)的急性心肌梗死(AMI)患者104例.最终采集了37个成年患者(＜65岁,成年组)和49个老年患者(≥65岁,老年组)的血液标本.在PCI治疗后的24 h和3d,检测比较血样中的ROS[丙二醛、髓过氧化物酶(MPO)和还原性谷胱甘肽(GSH)]和RNS[诱导型一氧化氮合酶(iNOS)活性、NOx(一氧化氮的氧化产物)和硝基化酪氨酸过氧亚硝酸阴离子(ONOO-)]水平.由于临床研究的局限,本研究设计了相应的动物实验,选取72只Sprague Dawley大鼠分为6组(青年大鼠鼠龄2个月,中年大鼠鼠龄10个月,老年大鼠鼠龄24个月;不同鼠龄各24只,同鼠龄鼠完全随机均分为两部分):青年空白对照组、中年空白对照组、老年空白对照组、青年缺血/再灌注组、中年缺血/再灌注组、老年缺血/再灌注组,每组12只.对不同鼠龄缺血/再灌注组大鼠进行心肌缺血/再灌注处理,左冠状动脉结扎30 min、再灌注24 h,3个空白对照组不进行结扎.采集大鼠缺血心肌组织/正常心肌组织和血液标本,检测心肌组织和血液标本中的ROS(丙二醛、MPO和GSH)和RNS(iNOS活性、NOx和硝基化酪氨酸ONOO-)水平,进行组间比较.结果 PCI术后24 h及术后3d老年患者血浆中丙二醛、MPO明显高于成年患者,GSH明显低于成年患者,差异有统计学意义[丙二醛:(8.6±2.3)μmol/L比(4.8±1.0) μmol/L、(7.5±1.8)μmol/L比(3.5 ±0.8)μmol/L,MPO:(707±224) μg/L比(474±126) μg/L、(667±187) μg/L比(377±114) μg/L,GSH:(2.6± 1.1) μmol/L比(3.7±1.0) μmol/L、(1.7±0.9) μmol/L比(2.5±1.1) μmol/L,P＜0.01];iNOS活性明显低于成年患者,差异有统计学意义[(28±11) pmol/(mg protein· min)比(34±9)pmol/(mg protein· min)、(20±8)pmol/(mg protein· min)比(24±8)pmol/(mg protein· min),P＜0.01].动物实验结果,趋势与临床研究基本一致.结论 衰老引起AMI患者及大鼠体内ROS和RNS的改变.
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