肝损伤是脓毒症患者常见的并发症，也是导致多器官功能衰竭的重要因素，研究证实改善肝脏能量代谢有助于减轻脓毒症肝损伤。申请者前期研究发现具有调节能量代谢功能的肝素结合表皮生长因子样生长因子（HB-EGF）对脓毒症肝损伤具有保护作用，但机制尚不清楚。解偶联蛋白2（UCP2）是线粒体内膜上的一种载体蛋白，参与肝脏的能量代谢，而过氧化物酶体增殖物激活受体α（PPAR-α）是UCP2的转录调控蛋白。申请者前期实验发现HB-EGF可上调脓毒症小鼠肝脏PPAR-α的表达。因此，申请者提出了“HB-EGF调控PPAR-α/UCP2信号改善肝脏能量代谢减轻脓毒症肝损伤”的假说。本项目拟采用PPAR-α基因敲除小鼠的脓毒症肝损伤模型和离体细胞模型来验证该假说，为寻找脓毒症肝损伤的防治策略提供理论依据。

Liver injury, usually occurring at early stage of sepsis, introduces the subsequent development of multiple organ failure. It has been well recognized that the improvement of hepatic energy metabolism can effectively alleviate sepsis-induced liver injury. Previously, we have found that the substance heparin binding epidermal like growth factor (HB-EGF) improves the hepatic energy metabolism in mouse developing sepsis-induced liver injury. However, the mechanism of how HB-EGF working requires the further study.The mitochondrial carrier protein uncoupling protein 2 (UCP2) plays a key role during hepatic energy metabolism. UCP2 is mainly regulated by the Peroxisome proliferator receptor-α (PPAR-α) transcriptionally in the mitochondria during sepsis. In our research, we have found that the expression of PPAR-α was up-regulated by HB-EGF in liver of septic mice. Collectively, we hypothesize that HB-EGF alleviates the sepsis-induced liver injury through it improving the hepatic energy metabolism by regulating the PPAR-α/UCP2 signal . The PPAR-α gene knockout mice will be employed in vivo (induced liver injury model) and in vitro (cell model) experiments to test the hypothesis. The findings in the project will advance our knowledge on the mechanism of sepsis-induced liver injury, and shall provide new protection strategy for sepsis-induced liver injury.