Role Of Aldehyde Dehydrogenase 2 In Acute Hyperglycemia Exacerbating Myocardial Ischemia/Reperfusion Injury In Rats

Backgroud:Recent studies have found that the incidence of hyperglycemia in the setting of acute myocardial infarction (AMI) be as high as 25%~50%, hyperglycemia is associated with increased myocardial infarction size and immediate and long-term poor prognosis expecially in non-diabetic AMI patients, indicating acute hyperglycemia is closely related to the poor prognosis of patients with AMI.Mitochondrial aldehyde dehydrogenase 2(ALDH2) is an important enzyme with genase and esterase enzyme function. In recent years, it was reported to provide protection against myocardial injury. Up-regulation of ALDH2 activity significantly reduced the myocardial infarct size and improved cardiac function. We previously found that diabetes-induced hyperglycemia inhibited ALDH2 activity and led to cardiac dysfunction. However it is unclear whether acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury through inhibiting aldehyde dehydrogenase 2 activity in rats.Objective:We established an acute hyperglycemia　& myocardial ischemia-reperfusion rat model to study the effect of acute hyperglycemia on ALDH2 activity and the role of ALDH2 in myocardial ischemia/reperfusion injury.Methods:Forty eight male Wistar rats were randomly divided into four groups:sham operation (SHAM) group, normal saline control (CON) group, high blood glucose (HG) group, and HG with Alda-1 administration (HG+Alda-1) group. The left anterior descending artery (LAD) was occluded for 30 minutes followed by １h reperfusion to establish the myocardial ischemia-reperfusion rat model. Acute hyperglycemia rat models were established via jugular vein injection of 50%　glucose (3g/kg) during the ischemia period. Blood glucose levels were maintained at 20- 28mmol/L throughout the experiment by administration of glucose with the trace pumping [4ml/(kg-h)] during ischemia and reperfusion period. The rats of CON group and HG+Alda-1 group were given normal saline (6ml/kg). The rats of HG+Alda-1 group were given Alda-1(8.5mg/kg) with the trace pumping during ischemia and reperfusion. After reperfusion, ALDH2 activity of the heart was detected by colorimetric method, the change of myocardial tissue morphology was observed with hematoxylin-eosin (HE) staining, myocardial infarction size was determined with TTC staining, and myocardial cell apoptosis was detected by TUNEL method.Result:1. Plasma glucose level in each group of rats:Plasma glucose level among groups before ischemia was not significantly different (P>0.05). Plasma glucose level was increased in CON group during ischemia and reperfusion but the difference was not significant (P>0.05). After injection of glucose via jugular vein, Plasma glucose level in HG group increased rapidly. Plasma glucose level was significantly increased in HG group and HG+Alda-1 compared with that in CON group during ischemia and reperfusion period [(23.4±0.21) mmol/L、(22.8±0.33) mmol/L vs (5.8±0.21) mmol/L, P<0.01 respectively].2. Myocardial ALDH2 activity in each group of rats:The activity of ALDH2 in CON group was lower than that in the SHAM group, but the difference was not significant [(87.0±4.30)% vs (100.0±3.91)%, P>0.05]. Compared with the SHAM and CON group, the activity of ALDH2 in HG group was significantly decreased [(69.1±5.16)% vs (100.0±3.91)%,(87.0±4.30)%, P<0.01, P<0.05, respectively], Compared with the HG group, the activity of ALDH2 in HG+Alda-1 group was significantly increased [(90.6.0±4.81)% vs (69.1±5.16)%, P<0.05]. The activity of ALDH2 in HG+Alda-1 group was similar to that in CON group [(90.6.0±4.81)% vs (87.0±4.30)%, P>0.05].3. Myocardial infarct size in each group of rats:Myocardial infarct size of CON group was significantly increased than that of SHAM group [(26.8±2.53)% vs (4.6±0.80)%, P<0.01]. Myocardial infarct size of HG group was significantly increased compared with the CON group [(38.2±3.3)% vs (26.8±2.53)%, P<0.05]. Compared with HG group, myocardial infarct size of HG+Alda-1 group was significantly decreased [(27.8±2.50)%　vs (38.2±3.30)%, P<0.05].Myocardial infarct size of in HG+Alda-1 group was similar to that in CON group[(27.8±2.50)% vs (26.8±2.53)%, P>0.05]。4. Myocardial apoptosis in each group of rats:The apoptosis of myocardial cell nucleus is brown. SHAM group accidental apoptosis of myocardial cells. The myocardial apoptosis index of CON group was significantly increased. Myocardial apoptosis index of CON group was significantly higher than that of SHAM group[(13.1±0.39)% vs (3.3±0.38)%, P<0.01].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 indext in HG+Alda-1 group was significantly decreased [(13.6±0.51)% vs (16.1±0.83)%, P<0.05]. Myocardial apoptosis index in HG+Alda-1 group was similar to that in CON group [(13.6±0.51)% vs (13.1±0.39)%, P>0.05].Conclusion:Acute hyperglycemia significantly inhibited ALDH2 activity as well as increased myocardial infarct size and myocardial apoptosis induced by myocardial ischemia-reperfusion injury; up-regulation of ALDH2 activity can significantly decrease myocardial infarct size and myocardial apoptosis during ischemia-reperfusion injury in acute hyperglycemia rats.