血红素氧合酶-1（HO-1）作为在应激状态下维持细胞和组织稳态最重要的保护因子之一，对肝脏缺血再灌注（I/R）损伤有明显的保护效应。我们的前期研究中发现大鼠肝脏缺血再灌注损伤后HO-1能促进肝脏微血管再生和内皮祖细胞（EPCs）功能活化，并伴随Notch信号相关基因上调。结果提示Notch信号在HO-1肝保护效应中起重要作用。据此我们推测：HO-1可能通过调控Notch信号通路活化内皮祖细胞，进而促进缺血再灌注损伤肝脏血管修复与再生。本课题拟借助HO-1基因敲除小鼠，从分子、细胞、组织以及动物水平等多层次明确HO-1对肝脏微血管内皮细胞缺氧后生物特性的影响及与Notch信号的关系，探讨HO-1对肝脏缺血坏死区血管修复与再生的影响，确定HO-1对Notch血管再生信号转导通路靶基因的调控，揭示肝脏缺血再灌注损伤过程中HO-1促进肝脏血管再生的机制，为肝脏I/R损伤临床防治探索可行的新途径。

Heme oxygenase-1 (HO-1), as one of the most importantly protective factors of maintaining cell and tissue homeostasis, has obvious protective effect for liver ischemia-reperfusion(I/R). Our previous study has found that HO-1 can promote hepatic microvascular regeneration and activation of endothelial progenitor cells (EPCs) in rat liver after ischemia-reperfusion injury, and Notch-related signal genes are up-regulated. The results suggest that Notch signaling plays an important role in HO-1 liver protection. Therefore, we hypothesized that HO-1 may activate endothelial progenitor cells by regulating Notch signaling pathway, and promote hepatic vascular repair and regeneration in liver ischemia-reperfusion injury. In this study, we will prepare to clarify the effects of HO-1 on the biological characteristics of hepatic microvascular endothelial cells after hypoxia and the relationship with Notch signaling from molecular, cellular, tissue and animal levels, with HO-1 knockout mice. We will investigate the effects of HO-1 on vascular repair and regeneration in hepatic ischemic necrosis, and determine the regulation of HO-1 on Notch angiogenic signal transduction pathway target genes. We will reveal the mechanism of HO-1 promoting hepatic vascular regeneration during hepatic ischemia-reperfusion injury, and explore a feasible new approach for clinical prevention and treatment of liver I/R injury.