Trx/TXNIP在脑卒中的研究进展

脑卒中是导致中老年人群死亡最主要原因之一,其具有较高的致死率和致残率,且每年的发病率呈逐年上升的趋势,严重危害人类的生命和健康,因此寻找有效的诊断及治疗脑卒中的靶点具有重要意义。硫氧还蛋白(Trx)是细胞内主要的硫醇还原剂,通过调节细胞内氧化还原状态,参与细胞内多种信号通路转导过程,具有二硫化物还原酶活性,通过抗氧化效应,减轻脑卒中后神经元氧化应激损伤。硫氧还原蛋白相互作蛋白(TXNIP)是Trx的内源性抑制剂,通过绑定/抑制Trx的活性,破坏细胞内氧化还原平衡,促进氧化应激,而抑制或敲除TXNIP具有明显的神经保护作用。最新研究表明Trx/TXNIP可经多种途径参与脑卒中病理生理过程。本文通过分析Trx和TXNIP的研究现状,以及探讨Trx系统在中枢神经系统中的定位和Trx系统在缺血性脑卒中的研究进展,展望Trx/TXNIP参与脑卒中的病理生理过程的信号途径,拟对Trx/TXNIP在脑卒中的作用机制进行综述,为脑卒中的治疗提供新思路。

Research Progress of Trx/TXNIP in Stroke

ABSTRACT: Cerebral apoplexy is one of the main causes of death in the middle-aged and elderly population, which has higher mortality and disability rate. The incidence of the disease is increasing year by year and it is a serious threat to human life and health. Therefore, it is of great significance to find an effective target for the diagnosis and treatment of stroke. Thioredoxin (Trx) is the major thiol reducing agent in the cells, it is involved in many signal transduction pathways in the cells by regulating the redox state of the cell.It has disulphide reductase activity, which can reduce the oxidative stress injury in the rats after the stroke. Thioredoxin interacting protein (TXNIP) is an endogenous inhibitor of Trx, it can destroy the redox balance and promote the oxidative stress by binding/inhibiting the ac- tivity of Trx, while the inhibition or knockdown of TXNIP has obvious neuroprotective effects. Recent studies suggest that Trx/TXNIP may be involved in the pathophysiology of cerebral apoplexy by a variety of pathways. This article analyses the research status of Trx/TXNIP and studies the localization of Trx system in the central nervous system and the progress of Trx system in ischemic cerebral apoplexy. It reviews the mechanism of Trx/TXNIP in cerebral apoplexy and prospectes the signaling pathways involved in the pathophys- iological process of Trx/TXNIP to provide new ideas for the treatment of cerebral apoplexy.