靶向线粒体:缺血性脑卒中的重要治疗策略

Targeting mitochondria:a vital therapeutic strategy for ischemic stroke

缺血性脑卒中(ischemic stroke,IS)是全球常见极具破坏性的神经系统疾病。尽管现代医学已认识到其病理进程中的部分机制,但这对IS治疗远远不够。近年研究证实,线粒体功能障碍在脑缺血后神经损伤中起着关键作用,是IS防治的潜在靶点。该文就脑缺血背景下线粒体稳态失调导致神经细胞损伤及死亡的主要分子机制进行综述,浅析线粒体通透性转换孔开放、氧化应激、凋亡信号传导的作用;同时以重塑线粒体功能为切入点,聚焦线粒体抗氧化剂、线粒体自噬调控、线粒体转移技术等线粒体干预或外源性治疗新方法,为IS防治提供新思路。

Ischemic stroke(IS)is a devastating neurological disease commonly around the world.Although modern medicine has recognized the confined mechanisms in the pathological process of cerebral ischemia,it has never been enough for the treatment of IS.Recent studies have confirmed the vital role of mitochondrial dysfunction in neuronal injury after cerebral ischemia,thereby exerting a potential target for prevention and treatment of IS.Herein,we review the main molecular mechanisms of neuronal injury and death by mitochondrial dyshomeostasis under the condition of ischemia/hypoxia,especially mitochondrial permeability transition pore opening,oxidative stress and apoptotic signaling.Given remodeling of mitochondrial function as a new idea for the management of IS,some emerging strategies containing mitochondrial antioxidant,mitophagy regulation and mitochondrial transfer also raise concern in this paper.