Comparison Between Effects Of AMP579 And Adenosine On Cardiomyocyte Apoptosis And NF-κB In Myocardial Ischemia-reperfusion Injury Rats

Objective:The purpose of this topic is studying protective effect of AMP579 and adenosine on cardiomyocyte apoptosis and NF-κB in myocardial ischemia-reperfusion injury rats, and comparing the differences between the two roles. Approaching AMP579 possible mechanism in ischemia-reperfusion, the purpose is to guide the AMP579 at clinical application.Methods:I/R model in vivo rats were established. Healthy male wistar rats (n=64) were divided into 4 groups:sham operation group (n=16):open the chest and braid without deligation the blood vessel, the anesthesia maintain 150min; ischemia-reperfusion group (I/R) (n=16):left anterior descending (LAD) occlusion for 30min and reperfusion for 120min, without any intervention; adenosine group (n=16):left anterior descending (LAD) occlusion for 30min and reperfusion for 120min, the group was given adenosine 305μg/kg-min for 5 min through the femoral vein before reperfusion; AMP579 group (n=16):left anterior descending (LAD) occlusion for 30min and reperfusion for 120min, the group was given AMP579 305μg/kg-min for 5 min through the femoral vein before reperfusion. TTC method was used to measure myocardial infarction area; HE stain method was used to observe cardiomyocyte by light microscope; TUNEL method was used to observe the number of apoptosis of each group; expression of NF-κB protein were observe by immunohistochemical technique.Result:1. The results of myocardial infarct size:Compared with sham-operated group rats (0), myocardial infarct size in I/R group (37.11±2.76)% was significantly increased (p<0.01). Compared with the I/R group, adenosine group(21.87±1.29)% and AMP579 group(18.96±1.19) % significantly reduced the infarct size (p<0.01), and AMP579 was better than adenosine (p<0.05).2. The degree of myocardial damage of adenosine group and AMP579 group is much litter than I/R group, and AMP579 group is litter than adenosine group.3. Compared with the sham-operation group (7.74±1.01)‰, the I/R group (439.83±13.93)‰has a higher rate of cardiomyocyte apoptosis (p＜0.Ol); Compared with the I/R group, adenosine group (312.57±11.93)‰and AMP579 group (268.33±10.84)‰significantly reduced the rate of cardiomyocyte apoptosis (p<0.01), and AMP579 group was lower than adenosine group (p<0.05).4. The results of NF-κB immunohistochemical staining:Compared with sham-operated group rats (0.073±0.013), NF-κB expression level in I/R group (0.416±0.064) was significantly increased (p<0.01). Compared with I/R group, NF-κB expression level in adenosine group (0.250±0.053) and AMP579 group (0.169±0.012) were significantly reduced (p<0.01), and AMP579 group was lower than adenosine group (p<0.05).Conclusion:Both adenosine and AMP579 can reduce myocardial infarct size and relieve myocardial ischemia-reperfusion injury. The one possible mechanism is inhibiting expression of NF-κB and relieve cardiomyocyte apoptosis. AMP579 has a better effect than adenosine.