SphK1/S1P信号通路在脑缺血再灌注神经细胞损伤机制中的研究进展

Progress of SphK1/S1P Signaling Pathway in the Mechanism of Cerebral Ischemia Reperfusion Injury

神经鞘磷脂及其代谢产物——神经酰胺、鞘氨醇(sphingosine,Sph)、鞘氨醇-1-磷酸(sphingosine-1-phosphate,S1P)作为重要的信号传递分子在细胞增殖、存活、凋亡及炎症免疫等病理生理过程中发挥重要作用,鞘氨醇激酶(sphingosine kinase,SphK)是催化Sph生成S1P的关键酶。脑缺血再灌注损伤涉及兴奋性毒性、神经炎症及氧化应激、自由基生成、血脑屏障损伤、细胞死亡等多种机制。本文主要阐述SphK1及S1P的功能特点,及脑缺血再灌注损伤涉及的机制,并进一步阐明目前关于SphK1/S1P信号通路在脑缺血再灌注神经细胞损伤中的作用及可能的分子机制。

Sphingomyelin and its metabolites [ceramide,sphingosine(Sph),sphingosine-1-phosphate(S1P)] being important signaling molecules play an very important role in pathophysiological processes such as cell proliferation,survival,apoptosis and immune response.Sphingosine kinase(SphK)is a key enzyme catalyzing Sph to S1P.Cerebral ischemia reperfusion injury involves various mechanism such as excitotoxicity,neuroinflammation and oxidative stress,free radical production,blood brain barrier injure,vascular permeability alteration and cell apoptosis.This article introduced the functional characteristics of SphK1 and S1P,the effect of SphK1/S1P signaling pathway on nerve cell injury in cerebral ischemia reperfusion and the possible molecular mechanism.