激活乙醛脱氢酶2抑制硝酸甘油耐受大鼠缺血再灌注心肌损伤  

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

作　　者：石曌玲[1] 殷玥[2] 余璐[3] 邢媛[2] 王衍帅[4] 李晨[4] 马恒[2] 

机构地区：[1]第四军医大学西京医院小儿科,陕西西安710032 [2]第四军医大学基础医学院生理学教研室,陕西西安710032 [3]第四军医大学西京医院病理科,陕西西安710032 [4]第四军医大学口腔医学系1队,陕西西安710032

出　　处：《心脏杂志》2013年第2期140-145,共6页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(81170108)

摘　　要：目的:探讨乙醛脱氢酶2(ALDH2)激动剂(Alda-1)对硝酸甘油耐受(NT)大鼠心肌缺血/再灌注损伤(MI/RI)的影响。方法:24只成年雄性SD大鼠随机分为4组:Con组、Alda-1组、NT组和NT+Alda-1治疗组,每组6只(n=6)。经静脉给予硝酸甘油10 mg/(kg.day)处理7 d,建立NT大鼠模型,治疗组在硝酸甘油给药的第5天起,同时输注Alda-1 10 mg/(kg.day)3 d。模型建立后,采用冠脉左前降支结扎缺血30 min再灌注4 h建立在体大鼠急性心肌缺血/再灌注(MI/R)模型。术中监测血流动力学指标,再灌结束后检测血清乳酸脱氢酶(LDH)并取心肌组织检测心肌梗死面积、蛋白质羰基化程度和心肌内活性氧簇(ROS)的水平。结果:离体血管灌流显示,硝酸甘油连续处理7 d,可导致大鼠血管内皮依赖性和内皮非依赖性舒张能力显著降低,提示出现NT。定量检测心肌AL-DH2的活性发现Alda-1可显著改善NT导致的心肌ALDH2活性抑制。在NT情况下,MI/RI较对照组显著加重,表现为心肌收缩舒张速率显著降低,血清LDH的水平显著增加,心肌梗死面积扩大(均P<0.05)。与NT组相比,采用Alda-1治疗,可显著改善NT组大鼠的MI/RI(均P<0.05)。并且,Alda-1治疗可显著抑制NT情况下缺血/再灌注心肌中蛋白质羰基化程度和ROS的含量。结论:激活ALDH2可显著抑制NT导致的MI/RI加重,其机制可能与减轻心肌蛋白质氧化损伤有关。AIM： To investigate the effect of acetaldehyde dehydrogenase 2 （ALDH2） agonist （ Alda-1 ） on the myocardial ischemia-reperfusion （MI/R） injury in nitroglycerin tolerant rats. METHODS： Male Sprague Dawley （SD） rats were randomized into control group （Con）, Alda-1 group （Aid）, nitroglycerin tolerant group （NTG） and Alda-1 treated NTG group （NTG ＋Ald）. Rats were treated with NTG for 7 days [ 10 mg/（kg .day） i. v. ] to establish the nitroglycerin tolerance model and the rats in treatment group were given Alda-1 β days, 10 mg/（ kg· day）] concomitantly with NTG from the fifth day. The left anterior descending artery （LAD） was occluded for 30 rain prior to 4 h reperfusion to establish the rat acute MI/R model. At the end of the 4-h reperfusion period, ALDH2 activities, reactive oxygen species （ROS） production, and myocardial protein carbonyl levels were measured and compared. RESULTS： Rats treated with NTG for 7 days caused marked tolerance as evidenced by impaired endothelium-depend-ent and -independent relaxation of aortic segments. Alda-1 treatment significantly improved cardiac ALDH2 activity under nitroglycerin tolerance. Compared with that of the control hearts, MI/R injury was signifi- candy enhanced in NTG hearts as evidenced by reduced ＋ LVdP/dtmax, increased serum lactate dehydro- genase （LDH） and accentuated infarct size （ P 〈 0. 05 ）. ALDH2 activator infusion effectively suppressed the above mentioned ischemic injury in the NTG hearts （ P 〈 0. 05 ） Alda-1 treatment significantly inhib- ited myocardial protein carbonylation and the content of ROS during MI/R in nitroglycerin tolerant ani- mals. CONCLUSIONS： Activating myocardial ALDH2 can significantly inhibit the MI/R injury accen- tuation caused by nitroglycerin tolerance and the cardioprotection of ALDH2 may partially mediate through inhibiting cardiac protein oxidative damage

关 键 词：乙醛脱氢酶2 硝酸甘油耐受 心肌缺血再灌注损伤 蛋白质羰基化 大鼠 

分 类 号：Q55[生物学—生物化学]