基于miR-378/Sirt1信号轴探讨circRNA在非酒精性脂肪性肝病炎症中的作用及衢枳壳黄酮干预机制

非酒精性脂肪性肝病（NAFLD）危害严重，且临床尚无有效的诊断和治疗靶标。衢枳壳黄酮（PTFC）防治NAFLD效果显著，但作用机理尚不明确。基于NAFLD痰瘀互结证及其治法，课题组前期研究发现，PTFC可以降低肝脏炎症反应，减轻肝组织脂肪病变，改善肝功能；miR-378在NAFLD中表达升高，通过靶向Prkag2调控sirt1，加剧炎症反应。生物信息学显示，circ_0010880与miR-378表达呈显著负相关，可通过ceRNA机制吸附miR-378。因此，本项目提出miR-378在NAFLD中调控炎症反应，其作用机制与circ_0010880竞争性结合相关，有望通过具有行气活血、祛痰散结功效的PTFC调控，成为干预NAFLD发展的新策略。拟从体内、体外两方面，利用分子生物学等技术明确PTFC通过miR-378调控NAFLD的作用机制，为NAFLD的临床治疗提供新思路。

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. However, there are no medications approved by the U.S. Food and Drug Administration, or China Food and Drug Administration for the treatment of NAFLD. Flavonoids from Citrus Paradisi cv.Changshanhuyou (PTFC) showed outstanding bioactivities in the prevention and treatment of NAFLD, however the mechanism of PTFC is still unclear. Based on NAFLD tanyu mutual syndrome and anti-NAFLD treatments, our previous study found that PTFC treatments could reduce liver inflammation, alleviate liver tissue fat lesions, and reverse degenerative phenotype. An increase of miR-378 will regulate Sirt1 to target Prkag2, which contribute to the inflammatory response in NAFLD. Bioinformatics showed that circ_0010880 was significantly negatively correlated with miR-378 expression, and miR-378 was adsorbed by ceRNA. Therefore, this project proposes that miR-378 regulates inflammatory response in NAFLD, relating to the competitive binding of circ_0010880. It is expected to be a new strategy for intervention in the development of NAFLD with PTFC treatments. It is planned to use molecular biology and other techniques to clarify the mechanism of PTFC on NAFLD through miR-378 from both in vivo and in vitro, and provide new ideas for the clinical treatment of NAFLD.