Zhao Baiyun, Zhang Jing, Zhao Kaiyue, Wang Bin, Liu Jing, Wang Chaoxuan, Zeng Ling, Zeng Xin, Luo Yan
Drug Clinical Trial Institution, Hangzhou Normal University Affiliated Hospital, Hangzhou, China; Department of Pharmacy， Hangzhou Normal University Affiliated Hospital, Hangzhou, China.
Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining, China.
J Pharm Biomed Anal. 2025 Jan 15;253:116541. doi: 10.1016/j.jpba.2024.116541. Epub 2024 Oct 22.
Rapamycin (Rapa) is an inhibitor of mTOR complex, and its therapeutic effect on liver function was examined in non-alcoholic fatty liver disease (NAFLD) rats here. And the possible mechanism of Rapa in NAFLD was preliminarily elucidated based on the non-targeted metabolomics analysis. Adult male SD rats were fed with a high-fat and high-cholesterol diet (HFD) to establish NAFLD model. For Rapa group, 0.8 mg/(kg.d) Rapa was given to the HFD rats. Ultra-performance liquid chromatography and Q-Tof-mass spectrometry (UPLC and Q-TOF/MS) analysis were applied for the identification of metabolites in the serum of rats, which were annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG). NAFLD rats presented with disturbed liver function, lipid metabolism and oxidative stress, but Rapa exerted a mitigating influence on the disorders. The metabolite profile data identified 579 metabolites that varied remarkably between the Rapa and HFD groups, with the main classes of amino acids and peptides, benzene, lipids and fatty acids. The differential metabolites were mainly involved in biosynthesis of cofactors, bile secretion, and glycerophospholipid metabolism were mainly enriched. In conclusion, Rapa has a potential protective effect against HFD-induced NAFLD, its hepatoprotective effect may achieved through mediating bile secretion and glycerophospholipid metabolism.
雷帕霉素（Rapa）是一种mTOR复合物抑制剂，本研究在此检测了其对非酒精性脂肪性肝病（NAFLD）大鼠肝功能的治疗作用。并基于非靶向代谢组学分析初步阐明了Rapa在NAFLD中的可能机制。成年雄性SD大鼠喂食高脂高胆固醇饮食（HFD）以建立NAFLD模型。对于Rapa组，给喂食HFD的大鼠给予0.8mg/（kg·d）的Rapa。应用超高效液相色谱和Q-TOF质谱（UPLC和Q-TOF/MS）分析鉴定大鼠血清中的代谢物，这些代谢物使用京都基因与基因组百科全书（KEGG）进行注释。NAFLD大鼠出现肝功能、脂质代谢和氧化应激紊乱，但Rapa对这些紊乱有缓解作用。代谢物谱数据鉴定出579种在Rapa组和HFD组之间有显著差异的代谢物，主要类别为氨基酸和肽、苯、脂质和脂肪酸。差异代谢物主要参与辅因子的生物合成、胆汁分泌，主要富集的是甘油磷脂代谢。总之，Rapa对HFD诱导的NAFLD具有潜在的保护作用，其肝脏保护作用可能通过介导胆汁分泌和甘油磷脂代谢来实现。
