FK506通过抑制CaN和ASK1信号回路对心肌缺血/再灌注损伤具有保护作用

ims: We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Methods and Results: Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506+Ischemia/reperfusion group (FK506-I/R), sham group and FK506+sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 mins and subsequently reperfusing for 120 mins. FK506 was administered 15 mins before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery and the blood supply was not blocked. I/R group showed a rapid increase of TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase of Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. Conclusions: FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.