蛋白激酶C和肾上腺素能受体参与大鼠心预处理保护机制

Norepinephrine precondition myocardium through activation of protein kinase C in rat heart

应用离休大鼠心脏灌流模型再次证实了缺血预处理可以减轻随后缺血再灌引起的心功能异常，并使冠脉流出液乳酸脱氨酶释放减少。观察到去甲肾上腺素可代替缺血预处理启动同等强度的心肌内源性保护效能。而应用蛋白激酶Ｃ抑制剂多粘菌素Ｂ可以阻断去甲肾上腺素预处理的保护作用。

Ischemic preconditioning(IPC) mechanism is related to adrenergic receptors and activation of protein kinase C(PKC). But the relationship between these two factors is not clear. The purpose of this study was to investigate the interaction between adrenergic receptors and PKC in ischemic preconditioning protection mechanisim. The control hearts,which were subjected to 30 minute global ischemia and 20 minute reperfusion without preconditioning, underwent severe myocardium injury. The percentage recovery of LV function index (LVSP-LVDP)×HR and±dp/dt max was only 35.1±4.4%, 42.0±4.3% and 40.9±5.4%,respectively, and the content of LDH in the perfusate was 1131.0±70.3 U/ml at 3 minute after reperfusion. The ischeniic preconditioning, 3 cycles of 5 minute ischemia and 5 minute reperfusion, made the injury much less than the control hearts. The percentage recovery of above LV function index was 87.7±7.8%, 92.3±6.1%, and 91.5±3.3%, respectively. The LDH release was reduced to 350.6±27.3U/ml ( P<0.01, IPC VS control). 5umol/L norepinephrine perfusion for 2 minutes followed by 10 minute washout could confer a similar protection as IPC. Addition of PKC antagonist polymyxin B 5 umol/L during norepinephrine perfusion and the 10 minute washout abolished the protection of norepinephrine preconditioning. The results suggest that adrenergic receptors initiate IPC protection through activation of PKC.