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缺血预处理-线粒体能量代谢偶联与心脏保护作用

IB-MECA and cardioprotection.

作者信息

Xu Zhelong, Jang Yeongho, Mueller Robert A, Norfleet Edward A

机构信息

Department of Anesthesiology, The University of North Carolina at Chapel Hill, NC, USA.

出版信息

Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):227-38. doi: 10.1111/j.1527-3466.2006.00227.x.

Abstract

The adenosine A(3) receptor plays an important role in ischemic preconditioning. Activation of the adenosine A(3) receptor with its agonists induces both early and late pharmacological preconditioning through various mechanisms. As the first potent and selective adenosine A(3) receptor agonist, IB-MECA (N(6)-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide) has been demonstrated to induce cardioprotection against myocardial ischemia/reperfusion injury when given before onset of ischemia by triggering pharmacological preconditioning. More importantly, IB-MECA can also protect the heart even when administered at the onset of reperfusion after ischemia, indicating a strong likelihood that the drug may be useful for the treatment of patients with acute myocardial infarction. However, since IB-MECA has been reported to have lethal effects at higher concentrations, and may cause systemic hypertension in some species, further studies are needed to find the best treatment strategy to increase its therapeutic potential.

摘要

腺苷A(3)受体在缺血预处理中发挥重要作用。用其激动剂激活腺苷A(3)受体可通过多种机制诱导早期和晚期药理学预处理。作为首个强效且选择性的腺苷A(3)受体激动剂,已证实IB-MECA(N(6)-(3-碘苄基)-腺苷-5'-N-甲基甲酰胺)在缺血发作前给药时,通过触发药理学预处理可诱导对心肌缺血/再灌注损伤的心脏保护作用。更重要的是,即使在缺血后再灌注开始时给药,IB-MECA也能保护心脏,这表明该药物极有可能对急性心肌梗死患者的治疗有用。然而,由于据报道IB-MECA在较高浓度时有致死作用,且在某些物种中可能导致全身性高血压,因此需要进一步研究以找到最佳治疗策略来提高其治疗潜力。

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