The Cardioprotective Effect Of Adenosine A2A Receptor Agonist After Coronary Mrcroemboembolization Through A P38 MAPK Signal Pathway

Object To investigate the cardioprotective effect of CGS21680 after coronary microembolization and its signal transduction.Methods Rats were chosen to perform the coronary microembolization.Time course and the peak time of P38MAPK(P38 mitogen-activated protein kinases) activity were determined by Western Blotting.Another 40 rats were randomly divided into Placebo group(P group),CGS21680 group(C group),SB203580(S group) and CGS21680+P79350 group(CP group).Saline,0.2 ug/kg CGS21680,0.2 ug/kg SB203580 or CGS21680+0.2ug/kg P79350 was administrated before the surgery.Cardiac function was determined by echocardiography. All rats were sacrificed at the peak time of P38MAPK activity.Then the activity of P38 MAPK and TNF-αmRNA expression in myocardium was correspondently determined by Western Blotting and RT-PCR.Result Time course of P38MAPK activity was determined by Westen Blotting.The dynamic changes of P38MAPK activity were observed.Phosphorylated P38MAPK(p-P38MAPK) was elevated at 1 hour after microembolization(versus at 0h after CME,P＜0.05).Then P38MAPK activity returned the level at baseline(versus at 0h after CME, P＞0.05).Therefore,it is 3 hours after CME that the time when P38MAPK activity and TNF-αmRNA expression in myocardium and LVEF was observed after intervention with agents.P38MAPK activity and TNF-αmRNA expression in myocardium in S group was significantly lower than those in P group(P＜0.05),whereas LVEF in S group was significantly higher than that in P group(P＜0.05).P38MAPK activity and TNF-αmRNA expression in myocardium in C group was also significantly lower than those in P group(P＜0.05),whereas LVEF in C group was significantly higher than that in P group(P＜0.05). P38MAPK activity and TNF-αmRNA expression in myocardium in CP group was significantly higher than those in S group & C group(P＜0.05) but not significantly different from that in P group(P＞0.05).LVEF in CP group was significantly lower than that in S group and C group(P＜0.05) but was not significantly different from P group(P＞0.05)Conclusion In the present study,it is investigated that the effect of adenosine A2A receptor agonist on the P38MAPK activity and TNF-αmRNA expression in rat myocardium and cardiac function.It was suggested that the activity of P38MAPK after CME was dynamic changed.Inhibition of P38MAPK could play a protective role in coronary microembolization.A protective effect of adenosine A2A receptor agonist on coronary microembolization may through a P38MAPK signal pathway.