首页|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

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

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

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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。
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,high&nbsp;blood 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 my-ocardial 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 peri-od.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 myo-cardial infarct size and myocardial apoptosis during ischemia-reperfusion injury in acute hyperglycemia rats.

Aldehyde dehydrogenase 2Acute hyperglycemiaRatsMyocardial ischemiaMyocardial reperfusion injury

李明华、王甲莉、徐峰、袁秋环、刘宝山、庞佼佼、张运、陈玉国

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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

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

乙醛脱氢酶 2 急性高血糖 大鼠 心肌缺血 心肌再灌注损伤

国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金泰山学者建设工程专项经费高等学校博士学科点专项科研基金山东省科技发展计划

81170136811001478130010381300219ts20130911201301311100482011GSF11806

2015

10.6040/j.issn.1671-7554.0.2014.852

山东大学学报(医学版)
山东大学

山东大学学报(医学版)

CSTPCD北大核心
影响因子：0.841
ISSN：1671-7554
年,卷(期)：2015.(5)
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