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缺氧缺血时神经元保护的新观点

冯源, 晁东满, 何小舟, 杨伊林, 康学智, Lawrence H LAZARUS5, 夏萤

耶鲁大学医学院，纽黑文 CT 06520，美国；南京医科大学第一附属医院， 南京 210029；苏州大学第三临床医学院，常州 213003；上海市针灸经络研究中心，上海 201203； 美国环境卫生科学研究院，NC 27709，美国

摘要

阿片类镇痛剂的临床应用具有悠久的历史。然而，阿片受体的功能，特别是其在脑内的作用，尚未完全阐明。 近年来，有关阿片受体介导的功能及其作用机制的研究，产生了大量新资料。其中，最令人兴奋的发现或许是δ 阿片受体 (δ-opioid receptor, DOR)对缺氧缺血神经元的保护作用。DOR 表达的上调和内源性阿片释放可增加神经元对缺氧缺血应激的耐 受性。根据应激的持续时间和严重程度的不同，DOR 信号可在多个水平触发不同机制，从而保护神经元，使之得以在应激 环境中生存。这些机制包括稳定离子内环境、增强促生存信号通路的转导(如PKC-ERK-Bcl2 通路)和增加抗氧化损伤的能力。 DOR 保护缺氧缺血神经元的最新资料，给神经保护并籍以对抗神经系统疾患的研究提供了一个新观念，对某些严重脑疾病(如 中风)的预防和治疗可能具有较大的意义。

关键词： 阿片肽; δ 阿片受体; 神经递质; 脑; 离子稳态; 神经保护; 低氧; 缺血

分类号：Q426

A novel insight into neuroprotection against hypoxic/ischemic stress

FENG Yuan, CHAO Dongman, HE Xiaozhou, YANG Yilin, KANG Xuezhi, Lawrence H LAZARUS, XIA Ying

Yale University School of Medicine, New Haven, CT 06520, USA； TheFirst Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China； The Third Clinical College of Soochow University, Changzhou 213003, China； Shanghai Research Center for Acupuncture and Meridians, Shanghai 201203, China； National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

Abstract

The use of opioid analgesics has a long history in clinical settings, although the functions of opioid receptors, especially their role in the brain, are not well understood yet. Recent studies have generated abundant new data on opioid receptor-mediated functions and the underlying mechanisms. The most exciting finding in the past decade is probably the neuroprotection against hypoxic/ischemic stress mediated by δ-opioid receptors (DOR). An up-regulation of DOR expression and the release of endogenous opioids may increase neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers, depending on stress duration and severity, different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of ionic homeostasis, an increase in pro-survival signaling (e.g., PKC-ERK-Bcl 2) and the enhanced anti-oxidative capacity. Recent data on DOR-mediated neuroprotection provide us a new concept of neuroprotection against neurological disorders and have a potentially significant impact on the prevention and treatment of some serious neurological conditions, such as stroke.

Key words: opioids; δ-opioid receptors; neurotransmitters; brain, ionic homeostasis; neuroprotection; hypoxia; ischemia;

收稿日期：2009-11-30　　录用日期：2009-12-16

通讯作者：夏萤　　E-mail: ying.xia@yale.edu

引用本文：

冯源, 晁东满, 何小舟, 杨伊林, 康学智, Lawrence H LAZARUS5, 夏萤. 缺氧缺血时神经元保护的新观点[J]. 生理学报 2009; 61 (6): 585-592.

FENG Yuan, CHAO Dongman, HE Xiaozhou, YANG Yilin, KANG Xuezhi, Lawrence H LAZARUS, XIA Ying. A novel insight into neuroprotection against hypoxic/ischemic stress. Acta Physiol Sin 2009; 61 (6): 585-592 (in Chinese with English abstract).