胍丁胺对家兔心肌缺血再灌注损伤的保护作用及其受体机制

CARDIOPROTECTIVE EFFECT OF AGMATINE ON MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN ANESTHETIZED RABBITS

目的研究胍丁胺 (agmatine ,AGM ) ,一种内源性可乐定置换物质 ,对家兔心肌缺血再灌注损伤的影响并分析其受体机制。方法在家兔心肌缺血 30min再灌注 180min模型上对心率、血压、心肌耗氧量、心外膜电图、心肌缺血面积及梗死范围进行记录并分析。结果在上述心肌缺血 再灌注模型上 ,AGM (10mg/kg)不仅降低心率、血压和心肌耗氧量 ,而且明显减小心肌梗死范围 ,说明AGM对心肌缺血再灌注损伤具有保护作用。应用咪唑啉受体和α2 肾上腺素能受体 (α2 adrenoceptor ,α2 AR)拮抗剂咪唑克生 (2mg/kg)可完全消除AGM的心肌保护作用。应用α2 AR阻断剂育亨宾 (1mg/kg)能部分阻断AGM的上述作用。用NOS抑制剂L NAME (5mg/kg)预处理并不影响AGM对心肌缺血再灌注损伤的保护作用。结论AGM能减小家兔心肌缺血再灌注损伤 ,此作用由α2 AR和咪唑啉受体共同介导。

ObjectiveTo investigate the effects of agmatine (AGM), an endogenous clonidine displacing substance (CDS), on myocardial ischemia reperfusion injury, and analyze its receptor mechanism(s) involved. MethodsAll experiments were performed on anesthetized rabbits by recording heart rate (HR), mean arterial pressure (MAP), epicardial electrocardiograph (EECG), myocardial risk area and infarct size in the model of 30 min regional coronary occlusion followed by 180 min reperfusion. ResultsAgm (10 mg/kg) not only reduced the HR, MAP and rate pressure product (RPP), but also decreased significantly myocardial infarct size in myocardial ischemia reperfusion model, indicating that Agm possess cardioprotective effects against myocardial ischemia reperfusion injury. The protective effects of Agm could be completely abolished by idazoxan (2 mg/kg), an α 2 adrenoceptor (α 2 AR) and imidazoline receptor (IR) antagonist, and be partially blocked by yohimbine (1 mg/kg), a selective α 2 AR antagonist.N G nitro L arginine methyl ester (L NAME, 5 mg/kg), a NOS inhibitor, did not affect the cardioprotective effects of Agm.ConclusionAgm exerts a cardioprotective effect against myocardial MI/R injury in anesthetized rabbits, which is mediated by α 2 AR and IR and may be related to the reduction in calcium influx.