AMPK/eNOS信号通路调控肝窦内皮细胞衰老在肝纤维化中的作用及机制

肝窦内皮细胞在肝脏纤维化发生和发展过程中起到关键作用。团队前期研究发现纤维化肝脏组织中，肝窦内皮细胞（LSECs）发生结构和功能改变，主要表现为LSECs衰老化。AMPK/eNOS通路可能通过调节LSECs衰老化进程，维持LSECs稳态，在延缓肝纤维化进展中具有重要作用，但其具体机制尚不清楚。本课题拟通过体内外实验，观察不同程度纤维化肝脏组织中，LSECs结构和基因表型变化，探讨LSECs衰老与肝纤维化发生发展之间的相互关系。通过LSECs与星状细胞（HSC）共同培养，观察衰老化肝窦内皮细胞对HSC激活的影响。构建肝硬化模型研究AMPK/eNOS通路在调控肝窦内皮细胞衰老过程中的作用，揭示其影响肝纤维化、肝硬化进程的具体机制。本项目研究的实施期望能够为肝纤维化的临床诊断与治疗提供新的思路和靶点。

Sinusoidal endothelial cells play a key role in the occurrence and development of liver fibrosis. Our previous research found that in fibrotic liver tissue, hepatic sinusoidal endothelial cells (LSECs) undergo structural and functional changes, mainly due to the senescence of LSECs. The AMPK/eNOS pathway may play an important role in delaying the progression of liver fibrosis by regulating LSECs senescence and maintaining the homeostasis of LSECs, but the specific mechanism is still unclear. This program intends to observe the relationship between LSECs structure and gene phenotype variations in different degrees of liver fibrosis through in vivo and in vitro experiments, and to explore the role of AMPK / eNOS signaling pathway in regulating the aging of LSECs. LSECs were co-cultured with stellate cells (HSC) to observe the effect of LSECs senescence on HSC activation. Liver cirrhosis model were conducted to further explore the role of AMPK/eNOS pathway in regulating LSECs senescence and maintaining normal morphology and function of LSECs in vivo. The implementation of the project research is expected to provide new ideas and targets for the clinical diagnosis and treatment of liver fibrosis.