脑出血后移植神经干细胞(NSCs)的存活、分化能力是影响NSCs治疗效果的关键因素。最新研究表明，泛素化结合蛋白SQSTM1/p62可以通过特定位点磷酸化激发p62-Nrf2之间“正反馈环路”，进而启动并放大Nrf2介导的内源性保护机制。本课题拟结合前期铁过载可以引起NSCs毒性损伤并诱导铁死亡负调控蛋白GPX4的表达下调，而干扰Nrf2表达则进一步减少GPX4的表达并加重铁离子毒性损伤的研究基础上，探讨并验证：1)NSCs铁过载损伤机制，明确铁死亡的发生；2)观察SQSTM1/p62基因表达调控对NSCs铁过载后铁死亡的影响，并阐明其相关分子机制；3)在脑出血环境中，通过基因转染等手段调控移植NSCs的SQSTM1/p62表达，观察移植NSCs的存活、分化能力以及小鼠脑出血后神经功能恢复情况。本课题研究将进一步拓展对关于脑出血后移植NSCs铁过载损伤机制的认识，并为脑出血治疗提供新思路。

The survival and differentiation of neural stem cells (NSCs) after transplantation is a key factor affecting the therapeutic effect of NSCs transplantation after intracerebral hemorrhage. Recent studies have shown that the ubiquitinated binding protein SQSTM1/p62 can activates the "positive feedback loop" between p62 and Nrf2 by the phosphorylation, and hereby initiating and amplifying the endogenous protection of the Nrf2 pathway. Based on the previous finding of iron overload could cause toxic damage to NSCs and induce down-regulation of ferroptosis negative regulatory protein GPX4 expression, and interfering the transcription factor Nrf2 further reduced GPX4 expression and increased iron toxicity, we will discuss and verify that: 1) Mechanism of iron overload injury in NSCs, and clarify the occurrence of ferroptosis; 2) Observe the effect of SQSTM1/p62 expression on ferroptosis after NSCs iron overload, and clarify its related molecular mechanism; 3) In the environment of ICH, regulating the expression of Nrf2 in transplanted NSCs by gene transfection, we will observe the survival and differentiation of transplanted NSCs and the recovery of neurological function after ICH in mice. This study will further expand the mechanism of iron overload injury in NSCs transplantation after ICH, and shed new lights on the treatment of ICH.