目的 明確龜齡集對輕度認(rèn)知功能障礙大鼠肝保護(hù)作用，并基于代謝組學(xué)技術(shù)揭示其潛在機(jī)制。方法 60只雄性SD大鼠隨機(jī)分為對照組、模型組和龜齡集高、低劑量（150、75 mg/kg）組、銀杏葉片（7.2 mg/kg）組及多奈哌齊（0.625 mg/kg）組。采用D-半乳糖合并半高脂飼料復(fù)制輕度認(rèn)知功能障礙大鼠模型，檢測各組大鼠肝臟指數(shù)、丙氨酸氨基轉(zhuǎn)移酶（alanine aminotransferase，ALT）、天冬氨酸氨基轉(zhuǎn)移酶（aspartate aminotransferase，AST）、堿性磷酸酶（alkaline phosphatase，ALP）水平，蘇木素-伊紅（hematoxylin eosin，HE）染色觀察肝組織病理變化；基于代謝組學(xué)篩選差異代謝物并進(jìn)行代謝通路分析。結(jié)果 與對照組比較，模型組大鼠肝臟出現(xiàn)病理損傷，并伴有肝臟指數(shù)下降、肝功指標(biāo)ALT和AST顯著升高（P＜0.05、0.01），ALP顯著下降（P＜0.05）；與模型組比較，龜齡集高劑量組和銀杏葉片組大鼠AST、ALT顯著降低（P＜0.05、0.01），龜齡集低劑量組ALT顯著降低（P＜0.01），多奈哌齊則對3項(xiàng)肝功指標(biāo)均無顯著調(diào)節(jié)作用。肝臟代謝組學(xué)發(fā)現(xiàn)23個差異代謝物，龜齡集可顯著回調(diào)所有差異代謝物，主要涉及的代謝通路包括嘌呤代謝，D-谷氨酰胺和D-谷氨酸代謝，精氨酸生物合成，丙氨酸、天冬氨酸和谷氨酸代謝，苯丙氨酸、酪氨酸和色氨酸生物合成。結(jié)論 龜齡集對輕度認(rèn)知功能障礙大鼠肝臟有顯著保護(hù)作用，且效果優(yōu)于銀杏葉片與多奈哌齊，其機(jī)制與調(diào)節(jié)氨基酸代謝和脂代謝密切相關(guān)。

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

山西省科技廳基礎(chǔ)研究計劃面上項(xiàng)目（202303021211175）；山西中醫(yī)藥大學(xué)博士科研啟動基金項(xiàng)目（2023BK39）；山西省研究生實(shí)踐創(chuàng)新項(xiàng)目（2023SJ269）；山西中醫(yī)藥大學(xué)科技創(chuàng)新團(tuán)隊(duì)（2022TD2007）；中藥生命組學(xué)與創(chuàng)新藥物研發(fā)研究室（zyyjs2024019）