NOS和PKC参与高铁血红素对心肌缺血/再灌注的防护作用

CARDIOPROTECTIVE EFFECTS OF NOS AND PKC UNDER HEMIN INDUCED ISCHEMIA/REPERFUSION INJURY IN RAT HEARTS

目的研究NOS和PKC在高铁血红素对抗心肌缺血/复灌损伤中的作用。方法采用离体大鼠心脏Langendorff灌流模型,观察心脏收缩功能、心肌梗死面积和酶学指标的变化。结果腹腔注射高铁血红素(50mg/kg)后24h,可明显改善缺血/复灌心脏(30min缺血,2h复灌)的收缩功能,减少复灌期LDH和CK释放,缩小心肌梗死面积。在腹腔注射高铁血红素前给予一氧化氮合酶(NOS)的抑制剂L-NAME可抑制高铁血红素对心肌损伤的防护作用。而蛋白激酶C(PKC)的抑制剂chelerythrine亦可阻断高铁血红素引发的心肌保护作用。结论高铁血红素可通过激活NOS和PKC,对抗心肌缺血/复灌性损伤。

Whether hemin, a heme oxygenase 1 （HO-1） inducer, reduces ischemia/reperfusion injury and whether NO synthase （NOS） and PKC are involved in the cardioprotective effects were investigated in the present study. Methods： The Langendorff model of isolated rat heart was used. The ventricular function, infarct size, LDH and CK during ischemia/reperfusion period were also ob-served. Results： ①After intraperitoneal injection of hemin（50 mg/kg） for 24 h, COHb concentration in rat blood enhanced. He-min preconditioning prevented the increase in LVEDP, decrease in LVDP and ± dP/dtmax in the isolated ischemia/reperfusion（ ischemia for 30 min and subsequent reperfusion for 2 h） rat hearts. The leakage of LDH and CK in the coronary effluent was significantly de-clined in hemin-treated rat hearts. And the infarct size was also reduced. ②By using an inhibitor of NOS NG-nitro-L-arginine methyl ester before the administration of hemin could inhibit the protection induced by hemin. ③Administration of an inhibitor of protein ki-nase C chelerythrine（ 1 mg/kg） before hemin preconditioning could also abolish the cardioprotection induced by hemin. Conclusion： These data suggest that the involvement of NO synthase and protein kinase C have been implicated in hemin-induced delayed cardio-protection in isolated rat hearts.