Protective effect of diazoxide preconditioning on ischemia and reperfusion isolated working rat heart

AIM To explore the mechanism of protection against myocardium ischemia/reperfusion (I/R) injury by diazoxide preconditioning (DPC). METHODS Isolated working heart models of Wistar rats were set up and were divided randomly into four groups. The I/R group (n=10): Equilibrium perfusion of 30 minutes was followed by a 60 minutes reperfusion. The DPC group (n=10) had a 10-min equilibration and two cycles of 5 min of 100 μm diazoxide perfusion followed by a 5-min diazoxide-free period before the 30 min ischemia and a 60-min reperfusion. The blank control group (n=3) and the dimethyl sulfoxide(DMSO) group (n=3) were perfused with the same treatment as in the DPC group, except that diazoxide was replaced with natriichloridum and DMSO. Frozen sections of myocardium at cardic apex were made and immunohistochemical staining was conducted to detect the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). 70 nm ultrathin sections were made and the mitochondria under each specimen was evaluated according to Flameng score. RESULTS The integrated optical density average (IODA) of PGC-1α expression was (8.40±3.64) in DPC group, (3.88±1.72) in I/R group,（3.40±2.44）in blank control and （3.69±1.92） in DMSO group. The expression of PGC-1α in DPC group was significantly higher than that in other groups（P<0.05）. Flameng score of was（1.78±0.14） in I/R group, （0.47±0.10） in DPC group, (1.69±0.23) in blank control and (1.72±0.17) in DMSO group, with significant difference between DPC group and other groups (P<0.01). CONCLUSION DPC can protect cardiomyocytes from ischemia and reperfusion injury, which may be related to the high expression of PGC-1α. PGC-1α may be an endogenous defense substance of myocardium.