激活乙醛脱氢酶2抑制老年大鼠心肌缺血再灌注损伤  

Acetaldehyde dehydrogenase 2 activation inhibits myocardial ischemia-reperfusion injury in senescent rats

作　　者：邢嫒[1] 殷玥[1] 石曌玲[2] 李晨[3] 王博文[3] 王衍帅[3] 高峰[1] 马恒[1] 

机构地区：[1]第四军医大学 生理学教研室,西安710032 [2]第四军医大学 西京医院儿科,西安710032 [3]第四军医大学 口腔医学系,西安710032

出　　处：《中华老年多器官疾病杂志》2013年第5期387-391,共5页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：国家自然科学基金（No.81170108）

摘　　要：目的衰老心肌对缺血／再灌注（I／R）损伤的耐受能力显著降低，导致老年心肌缺血易损性。本研究旨在探讨乙醛脱氢酶2（ALDH2）激动剂Alda-1对老年大鼠心肌I／R损伤的影响。方法成年（3～4月龄，40只）和老年（22～24月龄，40只）雄性SD大鼠随机分为I／R组和I／R＋Alda-1治疗组。采用冠状动脉左前降支结扎缺血30min再灌注4h建立在体大鼠急性心肌I／R模型，于再灌注前5min经静脉分别以2ml／（kg·h）速度分别输注生理盐水（0．9％NaCl）和Alda-1（16mg／kg）并持续到再灌注结束。于术中监测血流动力学指标，再灌注结束后取心肌组织检测ALDH2活性、蛋白质羰基化程度和心肌内活性氧簇（ROS）水平，抽取血样检测LDH水平。结果检测心肌ALDH2活性显示，老年心肌ALDH2活性较成年组显著降低。与成年组相比，老年心肌缺血再灌注损伤显著加重，表现为心肌收缩舒张速率显著降低，血清乳酸脱氢酶（LDH）水平显著增加（均P〈0．05）。再灌注期Alda-1治疗可有效提高老年I／R心肌ALDH2活性（P〈0．05），并显著抑制老年大鼠的上述心肌缺血再灌注损伤（均P〈0．05）。老年组I／R心肌中蛋白质羰基化程度和ROS生成较成年I／R心肌显著增加（均P〈0．05）。Alda-1治疗可有效改善老年I／R心肌中的蛋白质羰基化和ROS水平。结论激活心肌ALDH2可显著改善衰老心肌抗I／R损伤能力，其机制可能与减轻I／R导致的蛋白质氧化损伤有关。Objective Aging heart shows significantly reduced tolerance to myocardial ischemia/reperfusion （I/R） injury, so senescent heart is prone to be damaged by the injury. This study was designed to investigate the protective effect of acetaldehyde dehydrogenase 2 （ALDH2） agonist Alda-1 in aging rats after myocardial I/R injury. Methods A total of 40 aging male Sprague Dawley （SD） rats （at an age of 20 to 22 months） were randomized into I/R group （I/R） and Alda-1 group （I/R ＋ Alda）. Another 40 adult rats at an age of 3 to 4 months served as adult control. Rat acute myocardial I/R model was established by ligation of left anterior descending artery for 30min followed by reperfusion for 4h. Alda-1（16mg/kg） and normal saline at the same volume were intravenously infused at a flow rate of 2ml/（kg . h） into the left ventricle of corresponding rats in 5min before reperfusion. The left ventricular pressure was monitored at the same time. At the end of 4 hours reperfusion, ALDH2 activity, reactive oxygen species （ROS） production, and protein carbonylation in the myocardial tissue were measured. Serum level of lactate dehydrogenase （LDH） was tested. Results A significant decrease in ALDH2 activity was observed in the aging hearts, but this effect was blocked by Alda-1. Compared with the adult hearts, myocardial I/R injury was significantly aggravated in aging hearts, which were evidenced by reduced ＋ LVdP/dtmax and increased serum level of LDH （P 〈 0.05）. ALDH2 activator infusion during reperfusion effectively suppressed the above mentioned ischemic injury in the aging hearts （P〈 0.05）. Furthermore, protein carbonylation and ROS production in the myoeardium were increased in the aging hearts compared with the adult hearts （P 〈 0.05）, which was attenuated by Alda-1 treatment. Conclusion Activating myocardial ALDH2 significantly improves the resistance ability to myocardial I/R injury in aging heart. ALDH2-induced cardiac protection may be through suppressing myocardia

关 键 词：乙醛脱氢酶2 衰老 缺血再灌注损伤 蛋白质羰基化 活性氧簇 

分 类 号：R331.3[医药卫生—人体生理学] R592[医药卫生—基础医学]