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|本期目录/Table of Contents|

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

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第2期
页码:
140-145
栏目:
基础研究
出版日期:
2013-04-25

文章信息/Info

Title:
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
(第四军医大学：1.西京医院小儿科，2.基础医学院生理学教研室，3.西京医院病理科，4.口腔医学系1队，陕西 西安 710032)
Author(s):
SHI Zhao-ling1;  YIN Yue2;  YU Lu3;  XING Yuan2;  WANG Yan-shuai4;  LI Chen4;  MA Heng2
(1.Department of Paediatrics, Xijing Hospital, 2.Department of Physiology, 3.Department of Pathology, Xijing Hospital, 4.Team 1, School of Stomatology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
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
Keywords:
acetaldehyde dehydrogenase 2;  nitroglycerin tolerance;  myocardial ischemia-reperfusion injury;  protein carbonylation
分类号:
Q55
DOI:
-
文献标识码:
A
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-110 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ALDH2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。
Abstract:
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 (Ald), 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 ［3 days, 10 mg/(kg·day)］ concomitantly with NTG from the fifth day. The left anterior descending artery (LAD) was occluded for 30 min 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-dependent 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 significantly enhanced in NTG hearts as evidenced by reduced ±LVdP/dtmax, increased serum lactate dehydrogenase (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 inhibited myocardial protein carbonylation and the content of ROS during MI/R in nitroglycerin tolerant animals. CONCLUSIONS: Activating myocardial ALDH2 can significantly inhibit the MI/R injury accentuation caused by nitroglycerin tolerance and the cardioprotection of ALDH2 may partially mediate through inhibiting cardiac protein oxidative damage.

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备注/Memo

备注/Memo:
收稿日期：2012-10-25.基金项目：国家自然科学基金项目资助（81170108） 通讯作者：马恒，副教授，主要从事心肌内源性保护机制研究 Email:hengma@fmmu.edu.cn 作者简介：石曌玲，住院医师，硕士生 Email：szl0126@sina.com.cn 共同第一作者：殷玥，助理实验师 Email：music1021@126.com
更新日期/Last Update: 2013-04-28