S100家族A11在非酒精性脂肪性肝炎的作用及机制研究

非酒精性脂肪性肝炎（NASH）是非酒精性脂肪肝的疾病快速进展期，特征包括肝脏甘油三酯沉积、慢性炎症和持续性损伤。对NASH关键调控基因和信号通路的研究将揭示新的治疗途径和靶点。本课题组在前期工作中，首次发现在高脂喂养小鼠、ob/ob和db/db小鼠的肝组织中S100A11表达上调。进一步发现通过腺病毒过表达S100A11后，脂质沉积增加，甘油三酯合成基因表达上调，AKT-mTOR通路激活。提示S100A11可能通过AKT-mTOR通路参与脂质代谢过程，S100A11可能在NASH发生发展的过程中亦具有重要作用。因此，本项目将在这些重要发现的基础上，运用多种分子生物学方法，全面揭示S100A11在NASH发生发展中的作用和上下游调控机制，评估S100A11作为NASH干预靶点的有效性。本项目的实施，有助于进一步解析NASH的病理生理学机制，并为开发NASH治疗药物提供新的思路。

Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease, is characterized by liver triglyceride deposition, chronic liver inflammation, and persistent liver damage. Research on key regulatory genes and signaling pathways of NASH will reveal new therapeutic approaches and targets. In our previous work, we found for the first time that the expression of S100A11 levels were up-regulated in the liver tissues of high-fat fed mice, ob/ob and db/db mice. It was further demonstrated that adenovirus-mediated specific overexpression of S100A11 significantly increased lipid deposition, up-regulated triglyceride synthesis gene expression, and activated AKT-mTOR pathway. It is suggested that S100A11 may participate in lipid metabolism through the AKT-mTOR pathway, and play an important role in the development of NASH. Therefore, based on these important discoveries, this project will use a variety of molecular biological methods to comprehensively investigate the role of S100A11 in the development of NASH and its upstream and downstream regulatory mechanisms, and evaluate the effectiveness of S100A11 as a target for NASH treatment. The implementation of this project will not only help to further analyze the pathophysiology of NASH, but also provide new clues and theoretical basis for the development of NASH therapeutic drugs.