活性氧在移植肝缺血再灌注损伤（IRI）起关键作用，而相关的内源性抗氧化调控机制尚不清楚，近年发现Nrf2诱导抗氧化酶表达在IRI保护中起重要作用。而我们研究发现移植肝再灌注后Nrf2表达增强而抗氧化酶类表达和活性降低的分离现象，提示存在制约Nrf2作用的因素。新近发现Nrf2调节抗氧化酶表达需染色质重组复合物亚基Brg1参与；而我们预实验发现移植肝Brg1下调，尽管Nrf2表达增强却仍伴随严重的氧化损伤，丙泊酚后处理上调Brg1，促进Nrf2功能并减轻肝IRI。据此，我们设想Brg1/Nrf2通路激活在移植肝IRI和丙泊酚后处理保护中起关键作用。本课题拟用大鼠肝移植模型、供肝Brg1补充后移植模型、结合Brg1和Nrf2基因敲除鼠在体和细胞Brg1腺病毒转染后IRI模型等，及临床研究，阐明Brg1/Nrf2通路在移植肝IRI和丙泊酚后处理的作用及机制，为防治移植肝IRI提供理论及实验依据。

Reactive oxygen species induced oxidative damage plays a critical role in postoperative hepatic ischemia reperfusion injury(IRI) induced by orthotopic liver transplantation (OLT), however, the mechanism governing endogenous antioxidant regulation is unclear. In recent years, antioxidant enzymes expression induced by Nrf2 is considered to be a crucial event in protecting against oxidative damage. Of note, our preliminary study reveals that Nrf2 increases significantly after OLT but this does not result in enhanced function and expression of antioxidant enzymes. This unexpected disassociation between Nrf2 and endogenous antioxidant enzyme expression during Post-OLT liver IRI prompts us to postulate that there exists restricting factor(s) that affects Nrf2 normal functioning. Recent study indicates that the participation of Brg1, an ATPase subunit of the SWI/SNF chromatin remodelling complex, is mandatory for Nrf2 to induce endogenous antioxidant enzyme expression. Our preliminary experiment demonstrated that liver Brg1 was downregulated which was coincident with increased hepatic oxidative damage despite of the increase in liver Nrf2 expression, while propofol postcondition can upregulate Brg1 and enhance Nrf2 function and attenuated Post-transplantational liver IRI. Accordingly, we hypothesized that Brg1/Nrf2 signaling plays an important role in postoperative liver IRI induced by OLT and that activation of Brg1/Nrf2 signaling may represent a key mechanism of propofol postcondition protection. In our studies,we will use various models including in vivo rat model of OLT, hepatic IRI model respectively in Brg1 and Nrf2 knockout mice and in isolated cultured cells, in combination with Brg1 adenovirus transfection,and incorperate clinic reseach,in order to elucidate the role of Brg1, and in particular the role of Brg1/Nrf2 signaling in post-transplantational liver IRI and in propofol postcondition mediated protection.The proposed study will not only provide new mechanistic insight in post-transplantational liver IRI protection, but also provide experimental and practical guidance for the development of effective therapeutic strategies combating agaist liver IRI.