活性氧簇在脑缺血-再灌注损伤中的损伤与保护作用

The Disruptive Effects and Protective Effects of Reactive Oxygen Species in Cerebral Ischemia Reperfusion Injury

活性氧簇是细胞有氧代谢过程中产生的一类化学基团。线粒体是活性氧簇的主要生成位点。一般观点认为,在脑缺血-再灌注损伤过程中,活性氧簇发挥神经细胞损伤作用。活性氧簇不仅直接参与神经细胞氧化损伤过程,也可通过外源性途径和内源性途径,引起神经细胞凋亡。然而,除神经细胞损伤作用外,活性氧簇也可发挥神经细胞保护作用。活性氧簇可激活低氧诱导因子、核转录因子κB、PI3K/Akt通路和MAPK通路等,参与神经细胞存活机制,减轻神经细胞损伤。本文对活性氧簇在脑缺血-再灌注损伤中的双重作用进行综述。

Reactive oxygen species are a class of chemical groups which are produced during the aerobic metabolism in cells.At present,reactive oxygen species is mainly produced from mitochondria.In the physiological case,the reactive oxygen species generation and clearance maintain a dynamic balance.However,during the process of cerebral ischemia-reperfusion injury,the reactive oxygen species generation and removal has changed.In the ischemic period,the brain’s acidic environment promotes the reactive oxygen species production.And during the reperfusion period,the changes of the mitochondrial membrane potential hyperpolarization and pro-oxidase activity can also promote the reactive oxygen species production.In addition,during the process of cerebral ischemia-reperfusion injury,the brain’s ability to eliminate the reactive oxygen species also decreased.As a result,the generation of the reactive oxygen species increases.Reactive oxygen species has the dual functions in the process of cerebral ischemia-reperfusion injury.It is generally believed that reactive oxygen species play a role in neuronal injury during the cerebral ischemia-reperfusion injury.Reactive oxygen species can directly destroy the biological macromolecules including lipids,proteins and nucleic acids.Reactive oxygen species can also activate the extrinsic pathway and the intrinsic pathway leading to neuronal apoptosis.However,in addition to the role of neuronal injury,reactive oxygen species can also play a role in the protection of neurons.This may be related to the level of the reactive oxygen species,low levels of the reactive oxygen species can be used as signal molecules to promote cell survival.During the process of cerebral ischemia-reperfusion injury,reactive oxygen species can activate hypoxia inducible factor,nuclear factor kappa B,PI3K/Akt pathway and MAPK pathway,and participate in the survival mechanism of nerve cells and reduce the damage of nerve cells.In this paper,we will make a review about the dual functions of reactive oxygen species in the course of cerebral ischemia-reperfusion injury.