目的 通过非靶向代谢组学与脂质组学技术，分析急性酒精性肝损伤小鼠血清代谢产物及肝脏脂质分子，筛选酒精性肝损伤相关差异代谢物并进行通路富集及相关性分析，探究牛樟叶总多糖对急性酒精性肝损伤模型小鼠的肝脏保护作用机制。方法 以ig白酒建立小鼠急性酒精性肝损伤模型，设置对照组、模型组、水飞蓟宾(阳性药，100 mg·kg^-1)组及牛樟叶总多糖低、中、高剂量(100、200、400 mg·kg^-1)组；苏木素-伊红（HE）染色检测小鼠肝组织病理变化，试剂盒法检测血清三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）水平，同时采用非靶向代谢组学分析血清代谢物变化，脂质组学分析肝脏脂质分子变化，并对差异代谢物进行通路富集及相关性分析。结果 牛樟叶总多糖可显著改善模型小鼠肝组织脂肪变性、气球样变和坏死等病理损伤，且高剂量组与水飞蓟宾组肝组织结构基本恢复正常；牛樟叶多糖能剂量相关性降低血清TG、TC、LDL水平，提升HDL含量。血清代谢组学筛选出14个差异代谢物，涉及谷胱甘肽代谢及苯丙氨酸、酪氨酸、色氨酸生物合成等通路；肝脏脂质组学鉴定出28种显著调节的脂质分子，关联甘油磷脂、亚油酸、α-亚麻酸代谢通路。相关性分析发现L-谷胱甘肽等3种血清代谢物与肝脏脂质代谢物关联广泛，溶血磷脂酰胆碱（LPC）(18∶0)等4种脂质是连接肝脏局部损伤与全身代谢应答的关键分子。结论 牛樟叶总多糖对急性酒精性肝损伤小鼠具有显著的肝脏保护作用，其作用机制与调节脂质代谢通路、改善机体氧化应激状态、调控氨基酸代谢紊乱密切相关。

Objective To investigate the liver protective effect of total polysaccharides from Cinnamomum kanahirae leaves on acute alcoholic liver injury in mice by non-targeted metabolomics and lipidomics techniques, and to screen the related differential metabolites and construct metabolic pathways. Methods An acute alcoholic liver injury model in mice was established by intragastric administration of alcohol. The mice were divided into the control group, model group, silybin(positive drug, 100 mg·kg^-1) group, and low-, medium-, and high-dose total polysaccharides from C. kanahirae leaves(100, 200, and 400 mg·kg^-1) groups. Hematoxylin-eosin（HE） staining was used to detect pathological changes in the liver tissue of mice, and the levels of serum triglycerides（TG）, total cholesterol（TC）, low-density lipoprotein（LDL）, and high-density lipoprotein（HDL） were detected by kit method. Non-targeted metabolomics was used to analyze the changes in serum metabolites, and lipidomics was used to analyze the changes in liver lipid molecules. Pathway enrichment and correlation analysis were performed on the differential metabolites. Results Total polysaccharides from C. kanahirae leaves could significantly improve the pathological damage of liver tissues such as steatosis, ballooning, and necrosis in model mice, and the liver tissue structure in the high-dose group was basically restored to normal, similar to the silybin group. The polysaccharides could dose-dependently reduce serum TG, TC, and LDL levels and increase HDL content. Metabolomics of serum identified 14 differential metabolites, involving glutathione metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis pathways. Lipidomics of liver identified 28 significantly regulated lipid molecules, associated with glycerophospholipid, linoleic acid, and α-linolenic acid metabolism pathways. Correlation analysis revealed that three serum metabolites, such as L-glutathione, were widely associated with liver lipid metabolites, and four lipids, such as lysophosphatidylcholine（LPC）(18 ∶ 0), were key molecules connecting local liver injury and systemic metabolic responses. Conclusion Total polysaccharides from C. kanahirae leaves have a significant liver protective effect on acute alcoholic liver injury in mice, and the mechanism is closely related to the regulation of lipid metabolism pathways, improvement of oxidative stress status, and regulation of amino acid metabolism disorders.

R285.5;R575.5

广西研究生教育创新计划项目(YCSY2025096); 全国中药特色技术传承人才培训项目(T20234832005)