内源性一氧化氮在异氟醚抗心肌缺血再灌注损伤中的作用

The role of endogenous nitric oxide in mediating the protective effect of isoflurane against ischemia/reperfusion injury in isolated rat hearts

目的:研究内源性一氧化氮(NO)对异氟醚抗心肌缺血再灌注损伤作用的影响。方法:采用大鼠离体心脏Langendorff灌注模型。评价NO合成酶抑制剂L-NOARG和L-NAME对异氟醚保护心肌抵抗缺血再灌注损伤作用的影响。结果:异氟醚能显著增加冠脉流量(CF),促进缺血后再灌注期间心肌收缩功能和ATP含量的恢复。L-NOARG和L-NAME能完全拮抗异氟醚增加CF的作用,并且显著降低了异氟醚对缺血心肌的保护作用。M-受体阻断剂阿托品对异氟醚增加CF的作用无显著影响,但是显著降低了异氟醚的心肌保护作用。再灌注末,对照组和阿托品组心肌ATP含量显著低于其他治疗组(P<0.001);L-NOARG+异氟醚组和L-NAME+异氟醚组显著低于异氟醚组和阿托品+异氟醚Ⅰ组和Ⅱ组(P<0.05)。结论:内源性NO释放但不是M-受体介导的NO释放参与了异氟醚抗心肌缺血再灌注损伤的保护机制。异氟醚麻醉期间应用M-受体阻断剂有可能降低其心肌保护作用。

Objective:To study the role of endogenous nitric oxide in mediating the protective effect of isoflurane against ischemia/reperfusion injury.Method:The isolated Langendorff rat heart model was used to evaluate the effects of the nitric oxide(NO)synthesis inhibitor,NG-Nitro-L-Arginine(L-NOARG) and the muscarinic receptor antagonist-NO-synthesis inhibitor,Nitro-L-arginine methyl ester (L-NAME)on the protective effect of isoflurane against ischemia/reperfusion injury.Result:L-NOARG and L-NAME completely inhibited the increase in coronary flow(CF)indoced by isoflurane.The protective effects of isoflurane against ischemia/reperfusion injury were significantly attenuated by L-NOARG and L-NAME.Atropine did not prevent the increase in CF induced by isoflurne,but reduced the cardiac protective effects of isoflurane.Control group and atropine group showed lower cardal ATP content than other treated groups.The ATP content in L-NOARG+isoflurane,L-NAME+isoflurnae groups was lower than that of isoflurane group,atropine+isoflurane Ⅰ and Ⅱ groups.Conclusion:The L-arginine-nitric oxide or a related pathway but not muscarinic receptor,mediating release of NO,is involved in the mechanism by which isoflurane protects against ischemia/reperfusion injury.The block of muscarinic receptors may reduce the myocardial protection with isoflurane.