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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (5): 15-20.doi: 10.6040/j.issn.1671-7554.0.2014.852

• 基础医学 • 上一篇    下一篇

急性高血糖通过抑制ALDH2活性加重大鼠心肌缺血/再灌注损伤

李明华1,2, 王甲莉1, 徐峰1, 袁秋环1, 刘宝山1,2, 庞佼佼1,2, 张运2, 陈玉国1   

  1. 1. 山东大学齐鲁医院急诊科, 急性胸痛中心, 山东省卫生系统急危重症医学重点实验室, 山东 济南 250012;
    2. 教育部和卫生部心血管重构与功能研究重点实验室, 山东 济南 250012
  • 收稿日期:2014-11-21 修回日期:2015-03-18 出版日期:2015-05-10 发布日期:2015-05-10
  • 通讯作者: 陈玉国。E-mail:chen919085@126.com E-mail:chen919085@126.com
  • 基金资助:
    国家自然科学基金(81170136,81100147,81300103,81300219);泰山学者建设工程专项经费(ts20130911);高等学校博士学科点专项科研基金(20130131110048);山东省科技发展计划(2011GSF11806)

Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury by inhibiting aldehyde dehydrogenase 2 activity in rats

LI Minghua1,2, WANG Jiali1, XU Feng1, YUAN Qiuhuan1, LIU Baoshan1,2, PANG Jiaojiao1,2, ZHANG Yun2, CHEN Yuguo1   

  1. 1. Department of Emergency & Chest Pain Center, Qilu Hospital of Shandong University, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Jinan 250012, Shandong, China;
    2. Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Jinan 250012, Shandong, China
  • Received:2014-11-21 Revised:2015-03-18 Online:2015-05-10 Published:2015-05-10

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摘要： 目的 探讨乙醛脱氢酶2(ALDH2)在急性高血糖加重大鼠心肌缺血/再灌注(I/R)损伤中的活性变化及作用。方法 48只雄性Wistar大鼠随机分为假手术组(SHAM组)、盐水对照组(CON组)、高糖组(HG组)和高糖+Alda-1干预组(HG+Alda-1组),每组12只。采用左冠脉前降支(LAD)结扎缺血30 min,再灌注1 h,建立大鼠心肌I/R模型。在建立大鼠心肌I/R模型同时,经颈静脉给予首负荷剂量50%葡萄糖(3 g/kg),使大鼠血糖浓度迅速升高至20～28 mmol/L,持续微量泵入[4 mL/(kg·h)],使大鼠血糖浓度维持在20～28 mmol/L,至再灌注结束。SHAM组和CON组给予0.9%NaCl(6 mL/kg)。HG+Alda-1组给予Alda-1 (8.5 mg/kg)微量泵入,至再灌注结束。再灌注结束后取心脏,采用比色法检测ALDH2活性的变化,HE染色观察心肌组织形态学变化,TTC染色法检测心肌梗死面积,TUNEL法检测心肌细胞凋亡情况。结果 与CON组相比,HG组在缺血期和再灌注期血糖浓度明显升高[(23.4±0.21) vs (5.8±0.21) mmol/L, P<0.01]。HG组ALDH2活性明显低于CON组[(69.1±5.16)% vs (87.0±4.30)%, P<0.05]。HG组心肌梗死面积明显高于CON组[(38.2±3.30)% vs (26.8±2.53)%, P<0.05];HG+Alda-1组心肌梗死面积明显低于HG组[(27.8±2.50)% vs (38.2±3.30)%, P<0.05]。HG组心肌细胞凋亡指数明显高于CON组[(16.1±0.83)% vs (13.1±0.39)%, P<0.05];HG+Alda-1组心肌细胞凋亡指数明显低于HG组[(13.6±0.51)% vs (16.1±0.83)%, P<0.05]。结论 急性高血糖可加重I/R大鼠的心肌梗死面积及心肌细胞凋亡,使心肌ALDH2的活性降低;增强ALDH2活性可显著减少急性高血糖大鼠I/R后的心肌梗死面积及心肌细胞凋亡。

关键词: 急性高血糖, 大鼠, 心肌再灌注损伤, 心肌缺血, 乙醛脱氢酶2

Abstract: Objective To investigate the activity changes and actions of aldehyde dehydrogenase 2 (ALDH2) in myocardial ischemia/reperfusion injury exacerbated by acute hyperglycemia. Methods A total of 48 male Wistar rats were randomly divided into 4 groups: sham operation (SHAM) group, normal saline control (CON) group, highblood glucose (HG) group, and HG with Alda-1 administration (HG+Alda-1) group, with 12 animals in each group. The left anterior descending artery (LAD) was occluded for 30 minutes followed by 1 hour reperfusion to establish myocardial ischemia-reperfusion rat models. Acute hyperglycemia rat models were established via jugular vein injection of 50% glucose (3 g/kg) during the ischemia period. Blood glucose levels were maintained at 20-28 mmol/L throughout the experiment by administration of glucose with trace pumping[4 mL/(kg·h)] during ischemia and reperfusion period. The rats in CON group and HG+Alda-1 group were given normal saline (6 mL/kg). The rats in HG+Alda-1 group were given Alda-1 (8.5 mg/kg) with trace pumping during ischemia and reperfusion. After reperfusion, ALDH2 activity of heart was detected with colorimetric method, changes of myocardial tissue morphology were observed with HE staining, myocardial infarction size was determined with TTC staining, and myocardial cell apoptosis was tested with TUNEL method. Results Blood glucose level was significantly increased in HG group compared with that of CON group [(23.4±0.21) vs (5.8±0.21)mmol/L, P<0.01]. Compared with CON group, the activity of ALDH2 in HG group was markedly decreased [(69.1±5.16)% vs (87.0±4.30)%, P<0.05]. Myocardial infarct size of HG group was remarkably increased compared with the CON group [(38.2±3.30)% vs (26.8±2.53)%, P<0.05]. Compared with HG group, myocardial infarct size of HG+Alda-1 group was notedly decreased [(27.8±2.50)% vs (38.2±3.30)%, P<0.05]. Myocardial apoptosis index of HG group was significantly higher than that of CON group [(16.1±0.83)% vs (13.1±0.39)%, P<0.05]. Compared with HG group, myocardial apoptosis of HG+Alda-1 group was significantly reduced [(13.6±0.51)% vs (16.1±0.83)%, P<0.05]. Conclusion Acute hyperglycemia significantly increases myocardial infarct size and myocardial apoptosis induced by myocardial ischemia-reperfusion injury and reduced ALDH2 activity, while enhanced ALDH2 activity can markedly decrease myocardial infarct size and myocardial apoptosis during ischemia-reperfusion injury in acute hyperglycemia rats.

Key words: Acute hyperglycemia, Myocardial ischemia, Myocardial reperfusion injury, Aldehyde dehydrogenase 2, Rats

中图分类号: 

  • R541.4
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