缺血/缺氧预适应的神经保护作用研究进展

Research progresses in neuroprotective effects of ischemic/hypoxia preconditioning

有氧代谢对脑组织至关重要,神经系统对缺血/缺氧的耐受性差。内源性因素如缺血性卒中、癌症及外源性因素如高原暴露、航空作业、潜水等均会导致机体或器官的缺血/缺氧,从而引起中枢神经系统的功能紊乱以及病理改变。寻找提高脑低氧耐受性的策略对于增强机体适应低氧环境的能力及防治缺血/缺氧性疾病具有重要意义。大量研究表明,预先给予机体一个短时间的较轻程度的缺血/缺氧刺激,能够显著提高机体对随后更严重缺氧的耐受能力,这种现象被称为缺血/缺氧预适应。近年来,缺血/缺氧预适应作为一种诱导神经内源性保护的策略,受到了广泛关注,成为当前生物医学领域中的研究前沿和热点之一。到目前为止,缺血/缺氧预适应已经在多种临床前模型中进行了研究,如缺血性卒中、神经退行性疾病等。缺血/缺氧预适应的保护机制复杂,涉及低氧信号通路激活、抗氧化应激、抗炎、抗凋亡等多种效应。本文就目前报道的缺血/缺氧预适应的主要机制、基础及临床研究进展进行综述,以阐明缺血/缺氧预适应的神经保护作用及应用潜力。

The brain has poor tolerance to ischemia and hypoxia,which could result in dysfunction and pathological changes of central nervous system.Both endogenous factors such as ischemic stroke and cancer and exogenous factors such as plateau exposure,aviation,and diving can lead to ischemia and hypoxia of the body or organs.Therefore,it is of great significance to develop strategies to improve cerebral hypoxic tolerance to prevent from ischemic and hypoxic diseases.Many studies have shown that exposure to moderate ischemia and hypoxia in a short period of time can significantly strengthen the body's tolerance to subsequent more severe hypoxia.This phenomenon is known as ischemia/hypoxia preconditioning.As a neuroprotective strategy,ischemia/hypoxia preconditioning has become one of the hotspots in biomedical research,and it has been applied in a variety of preclinical models such as ischemic stroke and neurodegenerative diseases.The protective mechanism of ischemia/hypoxia preconditioning is complex,which involves hypoxia signaling pathway activation,antioxidant stress,anti-inflammatory,anti-apoptosis,and so on.In this work,we reviewed the protective mechanisms and the research progresses of ischemia/hypoxia preconditioning to highlight its application potential in the treatment of neurological diseases.