Protective effects of hypoxia inducible factor-1α on myocardial ischemia postconditioning in rats / 中国小儿急救医学

ABSTRACT

Objective:To investigate the protective role and mechanism of hypoxia inducible factor(HIF)-1α in myocardial ischemia postconditioning.Methods:Forty healthy adult SD rats were randomly divided into four groups with 10 rats in each group.The control group(group A)was sham operation group, and the rats underwent the same surgical procedures except that the suture passed under the left anterior descending branch(LAD)of the coronary artery was not tightened for 225 minutes.In the ischemia-reperfusion group(group B), the LAD was blocked for 45 minutes, and then reperfusion for 3 hours.In the ischemic postconditioning group(group C), 45 minutes after blocking the LAD, reperfusion was performed for 10 seconds-ischemia for 10 seconds at the beginning of reperfusion, a total of 3 cycles of intervention, and reperfusion for 3 hours.Ischemic postconditioning + HIF-1α inhibitor group(group D) 45 minutes after blocking the LAD, HIF-1α inhibitor AG490 (3 μg/g) was injected intraperitoneally, and reperfusion was performed for 10 seconds-ischemia 10 seconds at the moment of reperfusion.A total of 3 cycles of intervention, reperfusion for 3 hours.Blood samples were harvested from femoral vein at three time points(before ligation of the LAD, 45 minutes after ischemia, 3 hours after reperfusion)to analyze the serum levels of creatine kinase and cardiac troponin respectively.After 3 hours of reperfusion, myocardial tissue was used to measure the infarction size through 2, 3, 5-triphenyltetrazolium chloride staining method; and Western blot method was used to detect the expression of HIF-1α in each group.Results:(1) There were no significant differences in the serum levels of creatine kinase and cardiac troponin among four groups before ligation( P>0.05); 45 minutes after ischemia, there were significant differences between group B, group C, and group D compared with group A ( P<0.01). After 3 hours of reperfusion, there were significant differences between group B, group C, and group D compared with group A (all P<0.01), and group B, group D were significantly higher than that in group C ( P<0.05). (2)Compared with group A[(2.46±1.13)%], the area of myocardial infarction in group B was (45.81±5.96)%, in group C was (37.17±4.99)%, and group D was (45.00±3.29) %, and the differences were statistically significant ( P<0.01). (3)The HIF-1α protein in myocardial tissue in group A was slightly expressed; the expression of HIF-1α protein in group B was higher than that in group A( P<0.05); and group C was significantly higher than that in group B ( P<0.05); HIF-1α protein was almost not expressed in group D. Conclusion:After ischemic postconditioning, HIF-1α increased in myocardium; the increased expression of HIF-1α may be involved in the protective process of myocardial ischemic postconditioning in rats.