Protective effects of aldehyde dehydrogenase-2 mediated by PI3K/Akt signal pathway on acute myocardial infarction in mice with sub-acute alcoholism / 中华急诊医学杂志

ABSTRACT

Objective To evaluate the effects of sub-acute alcoholism on cardiac structure and function, and investigate the mechanisms of aldehyde dehydrogenases-2 (ALDH2)alleviating the damage of heart caused by acute myocardial infarction.Methods The wild mice with ALDH2 (+/+) (WT group) and mice with knockout type ALDH2 (-/-) genotypes (KO group) were raised and then divided into four groups according to the presence or absence of sub-acute alcoholism WT group (n=10), KO group (n=16), WT+alcoholism group(WT+E,n=10) and KO+alcoholism group(KO+E,n=10).The mice of WT+E group and KO+E group were fed with high-dose of ethanol(2 g/kg per day for 8 days), while the mice of WT group and KO group were treated with equal amount of saline instead.Acute myocardial infarction models were established in all mice after ethanol administration,and blood ethanol concentration, cardiac function, myocardial infarct size, the activity of ALDH2, and the key molecules of PI3K/Akt signal pathway and caspase-3 mRNA were detected one week after modeling.Statistical analysis was performed using SPSS 17.0.Differences in levels of detected biomarkers between groups were assessed using Chi-squared or One way ANOVA, and P<0.05 was considered to be statistically significant.Results (1) The mortality rates of WT group, KO group, WT+E group and KO+E group were 20.0%, 30.0%, 31.3% and 37.5%, respectively.(2)Compared with WT group and KO group, the blood ethanol concentration was higher and the damage of liver was more severe in WT+E group and KO+E group(P<0.05).(3)The fraction shortening of short axis of left ventricle(FS) and left ventricular ejection fraction were higher in WT group and WT+E group compared with KO group and KO+E group(P<0.05).(4) The area of myocardial infarction was largest in KO+E group, followed by KO group, WT+E group, and WT group (all P<0.05).(5) The activity of ALDH2 in WT group was higher than that in other groups, and the ALDH2 activity in KO+E group was lower than that in KO group (P<0.05).(6) There was no significant difference in expressions of PI3K among four groups.The level of p-Akt was highest in WT group, followed by WT+E group, KO group, and KO+E group (all P<0.05).The levels of caspase-3 mRNA was highest in KO+E group, followed by KO group, WT+E group, and WT group (all P<0.05).Conclusions Myocardial damage caused by acute myocardial infarction can be aggravated by sub-acute alcoholism, while ALDH2 protection can effectively alleviate the damage effects of sub-acute alcoholism on myocardial infarction.The mechanism of protective effects of ALDH2 on acute myocardial infarction may be related to attenuation of cardiocytes apoptosis mediated by PI3K/Akt signal pathway.