目的 明确龟龄集对轻度认知功能障碍大鼠肝保护作用，并基于代谢组学技术揭示其潜在机制。方法 60只雄性SD大鼠随机分为对照组、模型组和龟龄集高、低剂量（150、75 mg/kg）组、银杏叶片（7.2 mg/kg）组及多奈哌齐（0.625 mg/kg）组。采用D-半乳糖合并半高脂饲料复制轻度认知功能障碍大鼠模型，检测各组大鼠肝脏指数、丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）、碱性磷酸酶（alkaline phosphatase，ALP）水平，苏木素-伊红（hematoxylin eosin，HE）染色观察肝组织病理变化；基于代谢组学筛选差异代谢物并进行代谢通路分析。结果 与对照组比较，模型组大鼠肝脏出现病理损伤，并伴有肝脏指数下降、肝功指标ALT和AST显著升高（P＜0.05、0.01），ALP显著下降（P＜0.05）；与模型组比较，龟龄集高剂量组和银杏叶片组大鼠AST、ALT显著降低（P＜0.05、0.01），龟龄集低剂量组ALT显著降低（P＜0.01），多奈哌齐则对3项肝功指标均无显著调节作用。肝脏代谢组学发现23个差异代谢物，龟龄集可显著回调所有差异代谢物，主要涉及的代谢通路包括嘌呤代谢，D-谷氨酰胺和D-谷氨酸代谢，精氨酸生物合成，丙氨酸、天冬氨酸和谷氨酸代谢，苯丙氨酸、酪氨酸和色氨酸生物合成。结论 龟龄集对轻度认知功能障碍大鼠肝脏有显著保护作用，且效果优于银杏叶片与多奈哌齐，其机制与调节氨基酸代谢和脂代谢密切相关。

Objective To clarify the protective effect of Guilingji on the liver of mild cognitive impairment (MCI) rats, and reveal its potential mechanism based on metabolomics technology. Methods Sixty male SD rats were randomly divided into control group, model group, Guilingji high-dose group (150 mg/kg), Guilingji low-dose group (75 mg/kg), Ginkgo leaf tablets group (7.2 mg/kg) and donepezil group (0.625 mg/kg). The MCI rats was established by D-galactose combined with semi-high fat diet. Liver index, the level of glutamic-pyruvic transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected in each group, and hematoxylin eosin staining (HE) were used to observe the pathological changes of liver tissue. Based on metabolomics, differential metabolites were screened and metabolic pathways were analyzed. Results Compared with the rats in the control group, the rats in the model group had pathological liver injury, accompanied by a significant decrease in liver index, and the level of liver function indicators including ALT and AST were increased significantly (P < 0.05, 0.01), the level of ALP was decreased significantly (P < 0.05); Compared with the model group, the high-dose Guilingji group and the Ginkgo leaf tablets group showed significant reductions in AST and ALT levels in rats (P < 0.05, 0.01), and the low-dose Guilingji group exhibited a significant decrease in ALT levels (P < 0.01), donepezil had no significant effect on the liver function indexes. The liver metabolomics identified 23 differential metabolites, all of which could be significantly reversed by Guilingji. The main metabolic pathways included purine metabolism, D-glutamine and D-glutamate metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Conclusion Guilingji has a significant protective effect on the liver of MCI rats, and the effect is better than that of Ginkgo leaf tablets and donepezil. The mechanism is closely related to the regulation of amino acid metabolism and lipid metabolism.

R285.5

山西省科技厅基础研究计划面上项目（202303021211175）；山西中医药大学博士科研启动基金项目（2023BK39）；山西省研究生实践创新项目（2023SJ269）；山西中医药大学科技创新团队（2022TD2007）；中药生命组学与创新药物研发研究室（zyyjs2024019）