肝脏缺血-再灌注(I/R)损伤导致肝功能异常、急性肝衰竭、多器官功能衰竭甚至死亡。虽然实验室研究证实外源性雌激素对肝脏I/R有一定的保护作用，但其临床应用于肝脏I/R损伤仍存在争议。本课题组前期研究发现雌性小鼠肝脏热I/R后，参与雌激素代谢的关键硫酸化酶EST在肝组织表达显著上调，且与氧化损伤阶段重要的核转录因子Nrf2相关。为此我们提出假说：肝脏I/R中Nrf2激活导致EST上调，随即通过促进内源性雌激素代谢对机体造成损伤。为验证这一假说，本课题拟在前期基础上，开展以下研究：①肝脏I/R中EST上调对机体的影响及机制；②Nrf2影响EST上调的机制；③肝脏I/R中EST与Nrf2之间的反馈调节。本课题的完成，将帮助我们从调节内源性雌激素代谢方向入手，为临床、尤其女性患者肝脏I/R治疗提供新靶点，为开展肝脏I/R个体化防治提供新的思路。

Hepatic ischemia/reperfusion (I/R) injury presents with a spectrum of clinical manifestations ranging from asymptomatic elevation of liver enzymes to acute liver failure and death. Although laboratory studies demonstrated that exogenous estrogen may protect the organism against hepatic I/R injury, the clinical use of exogenous estrogens in hepatic I/R is still controversial. Our previous studies found that the expression of an important estrogen metabolizing enzyme, estrogen sulfotransferase (EST), was dramatically increased in the liver of female hepatic warm I/R models. And the induction was related to Nrf2, a transcriptional factor during oxidative stress. Therefore, we raise the hypothesis that during hepatic I/R, the activation of Nrf2 leads to the up-regulation of EST, hence causes liver injury by accelerating estrogen metabolism. For the validation of this hypothesis, our following study will comprise 3 parts: (1) to determine the impact of EST induction during hepatic I/R and the mechanisms; (2) to investigate the mechanisms of Nrf2 related EST induction in hepatic I/R; (3) to find out the feedback regulations between EST and Nrf2. The successful completion of the current study might provide a potential target to manage hepatic I/R by modulating endogenous estrogen metabolism in clinical setting, especially in females. It will also suggest new thread for personalized prevention and therapy for hepatic I/R injury.