The Effect Of Aldehyde Dehydrogenase2(ALDH2) On Myocardium Protection And Related Mechanism Research

Objective: To study the effects of aldehyde dehydrogenase2(ALDH2) on cardiacischemia and reperfusion injury in isolated perfused rat hearts; and study therelationship of aldehyde dehydrogenase2, nitric oxide (NO), and mitochondrialpermeability transition pore in myocardial injury. Methods: Male Sprague-Dawley ratswere randomly divided into: ischemia and Reperfusion (I/R); EtOH; cyanamide (CYA)and EtOH+CYA; NG-nitro-L-methyl arginine ester (L-NAME) and EtOH+L-NAME;EtOH+Atractyloside (EtOH+Atr). The rat hearts were subjected to30min regionalischemia (occlusion of left anterior descending artery) and120min reperfusion. Theventricular hemodynamic parameters were recorded, the lactate dehydrogenase (LDH)release and myocardial NO level were measured, myocardial infarct size were measuredby TTC staining. The gene expressions of ALDH2, Bcl-2and Bax were detected byRT-PCR. Results:1.Ventricular hemodynamic parameters: I/R group: duringreperfusion period, compared with baseline, LVDP,±dp/dtmax, HR, RPP were lower andLVEDP was higher. Compared with I/R group, EtOH group depressed the decrease ofLVDP,±dp/dtmax, HR, RPP and the increase of LVEDP (P<0.05~P<0.01); CYA groupfurtherly improved the decrease of LVDP,±dp/dtmax, RPP and the increase of LVEDP(P<0.05~P<0.01); the changes in EtOH+CYA group, EtOH+L-NAME group andEtOH+Atr group were similar to CYA (P<0.05~P<0.01).2. Lactate dehydrogenase(LDH): Compared with I/R group, EtOH group significantly reduced LDH release(P<0.01), CYA, EtOH+CYA group and EtOH+L-NAME group significantly increasedLDH release (P<0.01). Compared with EtOH group, EtOH+CYA group, EtOH+L-NAME group and EtOH+Atr group increased LDH release (P<0.01).3. Myocardialinfarct size: Compared with I/R group, EtOH group significantly reduced myocardialinfarct size (P<0.05), CYA, EtOH+CYA and EtOH+Atr group group significantlyincreased myocardial infarct size (P<0.01). Compared with EtOH group, EtOH+CYAgroup, EtOH+L-NAME group and EtOH+Atr group all increased myocardial infarctsize (P<0.01).4. NO levels in hearts: Compared with I/R, EtOH group, L-NAMEgroup and EtOH+L-NAME group reduced myocardial NO level (P<0.01). Comparedwith EtOH group, L-NAME group increased NO level (P<0.05); and EtOH+decreased NO level furtherly than EtOH group (P>0.05).5. RT-PCR detection: Compared withI/R group, the mRNA levels of ALDH2, Bcl-2in EtOH group were sharply increased(P<0.01), that of Bax was decreased (P<0.01); The mRNA levels of ALDH2, Bcl-2inCYA and EtOH+CYA group were sharply decreased (P<0.05~P<0.01), that of Bax wasincreased (P<0.05); The mRNA levels of ALDH2, Bcl-2in EtOH+Atr group weresharply decreased (P<0.05~P<0.01), that of Bax had no significant difference.Compared with EtOH group, the mRNA levels of ALDH2, Bcl-2in EtOH+CYA group,EtOH+L-NAME group and EtOH+Atr group were sharply decreased (P<0.01), thoseof Bax were increased (P<0.01). Conclusions: Increased ALDH2levels prevents theischemia and reperfusion injury and plays anti-apoptosis role, when ALDH2wasdecreased, ischemia and reperfusion injury and apoptosis happening were aggravated.The mechanism of ALDH2against myocardial injury maybe by related to reducemyocardial NO and inhibition of mitochondrial permeability transition pore opening.