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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2014年第5期

页码:

497-501

栏目:

基础研究

出版日期:

2014-05-25

文章信息/Info

Title:

Acetaldehyde dehydrogenase 2 inhibits protein oxidative damage and myocardial ischemia-reperfusion injury in diabetic mice

作者:

刘 军¹; 李 晨²; 殷 玥²; 余 璐³; 张利华¹; 马 恒⁴

(第四军医大学：1.唐都医院惠宾病房；
2.学员旅6队；
3.病理与病理生理学教研室；
4.生理学教研室；
陕西 西安 710032)

Author(s):

LIU Jun¹;  LI Chen²;  YIN Yue²;  YU Lu³;  ZHANG Li-hua¹;  MA Heng⁴

(1.Department of Geriatrics, Tangdu Hospital, 2.Team 6, Brigade of Cadets, 3.Department of Pathology, 4.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)

关键词:

乙醛脱氢酶2;  糖尿病; 缺血/再灌注损伤; 蛋白质羰基化

Keywords:

acetaldehyde dehydrogenase 2;  diabetes;  myocardial ischemia/reperfusion;  protein carbonyl

分类号:

R587.1

DOI:

-

文献标识码:

A

摘要:

目的:观察乙醛脱氢酶2 （ALDH2）激动剂Alda-1对Ⅰ型糖尿病（DM）小鼠心肌缺血/再灌注（I/R）损伤的影响，探讨羰基应激在DM心脏缺血性损伤易感性增高中的作用。方法: 以C57BL/6 雄性小鼠为实验对象，腹腔注射链脲佐菌素（STZ）制备Ⅰ型DM小鼠模型。将正常C57BL/6小鼠（20只）和DM小鼠（20只）随机分为I/R组和I/R+Alda-1治疗组，每组10只。采用冠状动脉左前降支结扎缺血30 min再灌注4 h建立在体小鼠急性心肌I/R模型，于再灌注前5 min经静脉以2 ml/（kg·h）速度分别输注生理盐水（NS）或Alda-1（16 mg/kg）并持续到再灌注结束。再灌注结束后取血检测血清乳酸脱氢酶（LDH）水平，取心肌组织检测ALDH2活性、心肌内活性氧簇（ROS）水平，蛋白羰基化程度和心肌梗死(MI)面积。 结果: 检测心肌ALDH2活性显示，DM小鼠心肌ALDH2活性较对照组显著降低。与对照组相比，DM小鼠心肌I/R损伤显著加重，表现为MI面积增大，血清LDH水平显著增加（均P<0.05）。再灌注期Alda-1治疗可有效提高DM小鼠I/R心肌ALDH2 活性（P<0.05），并显著抑制DM小鼠的上述心肌I/R损伤（均P<0.05）。DM组I/R心肌中蛋白质羰基化程度和ROS生成较对照组I/R心肌显著增加（均P<0.05）。Alda-1治疗可有效改善DM小鼠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DM小鼠心肌抗I/R损伤能力，其机制可能与减轻DM小鼠在I/R过程中导致的蛋白质氧化损伤有关。

Abstract:

AIM:To investigate the protective effect of acetaldehyde dehydrogenase 2 (ALDH2) agonist Alda-1 in diabetic mice after myocardial I/R injury. METHODS: Twenty diabetic mice were randomized into I/R group (I/R) and Alda-1 group (I/R+Alda). Another 20 C57BL/6 mice served as normal controls. Acute myocardial I/R mouse model was established by ligation of the left anterior descending artery for 30 min followed by reperfusion for 4 h. Alda-1(16 mg/kg) and normal saline at the same volume were intravenously infused at a flow rate of 2 ml/kg/h into the corresponding mice 5 min before reperfusion. At the end of the 4-h reperfusion, ALDH2 activity, reactive oxygen species (ROS) production, and protein carbonylation in the myocardial tissue were measured. Serum level of lactate dehydrogenase (LDH) was also measured and compared. RESULTS: A significant decrease in ALDH2 activity was observed in the diabetic hearts, but this effect was blocked by Alda-1. Compared with that in control hearts, myocardial I/R injury was significantly aggravated in diabetic hearts, which was evidenced by increased serum level of LDH and infarct size (P<0.05). ALDH2 activator infusion during reperfusion effectively suppressed the above-mentioned ischemic injury in the diabetic hearts (P<0.05). Furthermore, protein carbonylation and ROS production in the myocardium increased in the diabetic hearts compared with those in the control hearts (P<0.05), which was attenuated by Alda-1 treatment. CONCLUSION: Activating myocardial ALDH2 significantly improves the resistance ability against myocardial I/R injury in diabetic hearts. ALDH2-induced cardiac protection may result from suppressing myocardial I/R-induced protein oxidative damage.

参考文献/References

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备注/Memo

备注/Memo:

收稿日期：2013-12-31.
基金项目：国家自然科学基金资助项目（81170108,31201037，81322004）;国家优秀青年科学基金资助项目(81322004)
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：刘军, 主治医师，博士 Email：liujunxn@ fmmu.edu.cn

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更新日期/Last Update: 2014-06-05