肝实质离断联合门静脉结扎的二步肝切除术（ALPPS）可以诱导术后肝脏快速再生解决大范围肝切除术后肝衰竭的困境，然而其诱导肝再生的具体调控机制尚未阐明。前期研究发现总胆汁酸水平在不同增生速率的ALPPS患者中存在差异,动物模型ALPPS术后胆汁酸/FXR通路明显激活上调，推测ALPPS手术可能改变了胆汁酸的肠肝循环路径，促进该通路激活，进一步研究发现：肝脏线粒体损伤相关分子模式（Mito-DAMP）的血清水平在ALPPS术后明显增加，而术前使用FXR激动剂预处理可以增加术后Mito-DAMPs的血清水平。由此推测：胆汁酸/FXR通路通过调控Mito-DAMPs从肝脏释放可能是促进ALPPS术后肝脏再生的重要机制。.本项目拟从细胞、动物及临床水平，利用qRT-PCR、免疫组化等实验方法进一步验证其具体调控机制。项目的开展有望为肝切除术后肝衰竭高风险的患者提供新术前评估指标和围术期治疗靶点。

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can induce rapid liver regeneration which help to solve the dilemma of liver failure after large liver resection. However, the mechanism for liver regeneration after ALPPS has not yet been well elucidated. The role of ALPPS in the fibrosis liver remains unclear..Clinical studies have found that total bile acid levels are different among patients with different proliferation rates before ALPPS which may indicate that nuclear receptor FXR plays an important role in promoting liver regeneration. Our study in a fibrotic ALPPS mouse model found that the bile acid / FXR pathway was significantly up-regulated after ALPPS. It is speculated that ALPPS may change the enterohepatic circulation of bile acid and make bile acid enriched in the future liver remnant (FLR ), Promoting the activation of FXR pathway, and further research found that the liver mitochondria-related damage associating molecular patterns (Mito-DAMP) in serum increased significantly after ALPPS, which was basically consistent with the Ki-67 expression of liver cells after surgery. Pretreatment of Mdr2-/-FVB mice with FXR agonist OCA can increase the serum level of Mito-DAMPs after transection. Therefore, we speculated that the release of Mito-DAMPs mediated by bile acid / FXR pathway may induce liver regeneration after ALPPS. .In the present project, we will further explore the function of Mito-DAMPs on liver regeneration in vitro and especially in vivo experiments.Further, wtih using qRT-PCR, immunohistochemistry and other methods,we want to clarify the relationship between Mito-DAMPs and FXR pathway. The project is expected to provide new evaluation indicators and perioperative therapy targets for patients at high risk for liver failure.