乙醇摄入对乙醛脱氢酶2不同基因型小鼠急性心肌梗死及DNA氧化损伤的影响

Effects of aldehyde dehydrogenase-2 on acute myocardial infarction and DNA oxidative damage induced by ethanol intake in mice

目的探讨大剂量乙醇摄入对乙醛脱氢酶2(ALDH2)不同基因型小鼠急性心肌梗死及DNA氧化损伤的影响。方法将23只ALDH2基因敲除型(KO)和19只野生型(WT)小鼠随机分为4组:KO组11只,KO+乙醇(E)组12只,WT组9只,WT+E组10只,其中KO+E组及WT+E组经口灌胃大剂量乙醇[2g/(kg·d),连续8d],而KO组及WT组每日经口予以等量0.9%氯化钠溶液连续8d。所有小鼠均制备急性心肌梗死模型,建模4周后经超声诊断仪检测心功能,采用伊文蓝颜料测定心肌梗死面积,E LISA法测定心肌8-羟基脱氧鸟苷(8-OHdG)水平。结果(1)急性心肌梗死造模后4周,KO组、KO+E组、WT组、WT+E组小鼠存活数量分别为7、8、7、7只,病死率分别为18.2%、33.3%、22.2%、30.0%,4组间差异无统计学意义(P>0.05)。(2)WT组小鼠左室短轴缩短率、射血分数均高于KO组小鼠,4组间差异均有统计学意义(均P<0.05)。(3)心肌梗死面积由大至小依次为:KO+E组>KO组>WT+E组>WT组,4组间差异均有统计学意义(均.P<0.05)。(4)心肌8-OHdG水平由高至低依次为:KO+E组>KO组>WT+E组>WT组,4组间差异均有统计学意义(均P<0.05)。结论增强ALDH2表达可有效地拮抗大剂量乙醇摄入对急性心肌梗死的损害作用,其发挥保护作用的机制可能与减轻心肌细胞DNA氧化损伤有关。

Objective To investigate the effects of aldehyde dehydrogenase-2 （ALDH2） on myocardial infarction and DNA oxidative damage induced by ethanol intake in mice. Methods The mice with ALDH2（^＋/＋） （WT group） and ALDH2 ^（-/-） genotypes （KO group） were raised and then divided into two subgroups with or without ethanol treatment： KO group （n=11）, WT group （n=9）, KO ＋ ethanol group（n=12） and WT ＋ ethanol group（n=10）. The KO ＋ ethanol group and WT ＋ ethanol group were fed with high dose of ethanol, while the KO group and WT group were treated with equal volume of saline. Acute myocardial infarction was induced in all mice; 4 weeks later then the cardiac function were detected by ultrasonography, the myocardial infarct size was measured by Evan＇s blue pigment, and myocardial 8-hydroxy-2＇-deoxyguanosine （8-OHdG） level was determined by ELISA. Results The mortality rates of KO group, WT group, KO ＋ ethanol group and w-r ＋ ethanol group were 18.2%, 33.3%, 22.2% and 30.0%, respectively （P 〉0.05）. The fraction shortening of left ventricular and ejection fraction were higher in WT group compared to KO group （P〈0.05）. The area of myocardial infarction was the largest in KO＋ ethanol group, followed by KO group, WT ＋ ethanol group, and WT group （all P〈O.05）. The revels of 8-OHdG was highest in KO ＋ ethanol group, followed by KO group, WT＋ethanol group, and WT group （all P〈0.05）. Conclusion Enhanced ALDH2 gene expression may effectively protect myocardium from infarction caused by high dose ethanol intake, which may be related to its attenuation of myocardial oxidative damage.