基于缺血性脑卒中再灌注损伤机制的抗氧化纳米药物研究进展

Research Progress of Antioxidant Nanotherapeutics against Ischemic Stroke Based on the Mechanism of Ischemia-Reperfusion Injury

在缺血性脑卒中-再灌注过程中,活性氧异常增多引起的脑组织神经元氧化应激是脑缺血-再灌注损伤的最主要病理机制。快速恢复脑组织血流灌注,同时抑制神经元氧化损伤是治疗缺血性脑卒中的有效途径。目前抗氧化类药物存在生物利用率低、作用方式单一及副作用大等缺点,极大限制了其疗效与临床应用。近年来,纳米药物因其尺寸、形貌可控及表面可修饰性等优势,在生物应用中展现出良好的应用前景,有望突破缺血性脑卒中神经保护类药物开发的瓶颈。重点阐明脑缺血-再灌注损伤的机制,综述抗氧化纳米药物的设计合成及其逆转神经元氧化损伤的作用机制与应用,为防治缺血性脑卒中提供新的思路。

The main pathogenic mechanism of ischemic stroke-reperfusion injury is neuronal oxidative stress induced by aberrant increase in reactive oxygen species during the ischemic stroke-reperfusion process.Restoration of blood flow in cerebral tissue while inhibiting neuronal oxidative damage would be an effective way to treat ischemic stroke.Currently,the efficacy and application of clinical antioxidant drugs are greatly restricted by their low bioavailability,single mode of action,and serious side-effects.In recent years,nanomedicines have shown promising biological applications due to their controllable size and morphology and high surface modification,which are expected to break the bottleneck in the development of neuroprotective drugs for ischemic stroke.This review elucidates the mechanism of cerebral ischemia-reperfusion injury and summarizes the design and synthesis of antioxidant nanomedicines,their mechanism of action and application in reversing oxidative damage in neurons,which will provide a new strategy for the prevention and treatment of ischemic stroke.