海马乙醛脱氢酶2在大鼠心肌缺血再灌注后记忆功能减退中的作用  

Role of acetaldehyde dehydrogenase 2 in hippocampus in memory decline after myocardial ischemia-reperfusion in rats

作　　者：杨文曲[1] 于菁[1] 王慧[1] 韩冲芳[1] 贺建东[1] 段应磊 裴若萌 Yang Wenqu;Yu Jing;Wang Hui;Han Chongfang;He Jiandong;Duan Yinglei;Pei Ruomeng(Department of Anesthesiology,Third Hospital of Shanxi Medical University,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Taiyuan 030032,China)

机构地区：[1]山西医科大学第三医院(山西白求恩医院,山西医学科学院,同济山西医院)麻醉科,太原030032

出　　处：《中华麻醉学杂志》2022年第9期1072-1075,共4页Chinese Journal of Anesthesiology

基　　金：山西省青年科技研究基金(201901D211509)。

摘　　要：目的评价海马乙醛脱氢酶2(ALDH2)在大鼠心肌缺血再灌注后记忆功能减退中的作用。方法健康雄性SD大鼠24只,2~3月龄,体重220~280 g,采用随机数字表法分为3组(n=8):假手术组(S组)、心肌缺血再灌注组(I/R组)和ALDH2激动剂ALDA-1组(ALDA-1组)。采用结扎左冠状动脉前降支30 min再灌注120 min的方法制备心肌缺血再灌注损伤模型。ALDA-1组于缺血前5 min腹腔注射ALDA-110 mg/kg。于造模前6 d开始进行Morris水迷宫定位航行训练,模型制备后24 h进行Morris水迷宫空间探索实验。行为学实验结束以后处死大鼠,取海马组织,HE染色观察病理学结果,TUNEL法确定细胞凋亡指数(AI),比色法检测ALDH2活性,ELISA法检测4-羟基壬烯酸(4-HNE)和MDA含量,Western blot法检测ALDH2和4-HNE的表达水平。结果与S组比较,I/R组穿越原平台位置次数减少,目标象限停留时间缩短,海马组织ALDH2活性降低,4-HNE表达上调,4-HNE、MDA含量和AI升高(P<0.05);与I/R组比较,ALDA-1组穿越原平台位置次数增加,目标象限停留时间延长,ALDH2活性升高,4-HNE表达下调,4-HNE、MDA含量和AI降低(P<0.05);3组海马组织ALDH2表达差异无统计学意义(P>0.05)。结论大鼠心肌缺血再灌注后记忆功能减退的发生机制可能与海马ALDH2活性降低,促进醛类物质蓄积有关。Objective To evaluate the role of acetaldehyde dehydrogenase 2(ALDH2)in hippocampus in memory decline after myocardial ischemia-reperfusion(I/R)in rats.Methods Twenty-four healthy male Sprague-Dawley rats,aged 2-3 months,weighing 220-280 g,were divided into 3 groups(n=8 each)using a random number table method:sham operation group(group S),myocardial I/R group(group I/R)and ALDH2 agonist ALDA-1 group(group ALDA-1).Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion in anesthetized animals.ALDA-110 mg/kg was intraperitoneally injected at 5 min before ischemia in group ALDA-1.The positioning navigation training in Morris water maze test was started from 6 days before developing the model.The spatial exploration in Morris water maze test was performed at 24 h after developing the model.The rats were sacrificed after the end of behavioral experiment,and the hippocampus was extracted for microscopic examination of the pathological changes(by hematoxylin and eosin staining)and for determination of the apoptosis index(AI)(by TUNEL staining),activity of ALDH2(by colorimetry),contents of 4-hydroxynonenal(4-HNE)and malondialdehyde(MDA)(by enzyme-linked immunosorbent assay),and expression of ALDH2 and 4-HNE(by Western blot).Results Compared with group S,the number of crossing the original platform was significantly decreased,the time spent in the target quadrant was shortened,the activity of ALDH2 in the hippocampus was decreased,the expression of 4-HNE was up-regulated,and the contents of 4-HNE and MDA and AI were increased in group I/R(P<0.05).Compared with group I/R,the number of crossing the original platform was significantly increased,the time spent in the target quadrant was prolonged,the ALDH2 activity was increased,the expression of 4-HNE was down-regulated,and the contents of 4-HNE and MDA and AI were decreased in group ALDA-1(P<0.05).There was no significant difference in ALDH2 expression in hippocampus among the three groups(P>0.05).

关 键 词：醛脱氢酶 心肌再灌注损伤 认知功能障碍 

分 类 号：R614[医药卫生—麻醉学]