目的 应用代谢组学技术，探究蒙古扁桃石油醚提取物对肝纤维化病程中代谢轮廓及生物标志物的影响，从代谢角度揭示其抗肝纤维化的作用机制。方法 大鼠连续8周sc四氯化碳（CCl₄）建立肝纤维化模型，同时ig蒙古扁桃石油醚提取物（1.75、1.25、0.75 g/kg）或水飞蓟素（50 mg/kg）。采用超高效液相色谱与四极杆-飞行时间串联质谱（UPLC-Q-TOF/MS）联用技术，分析各组大鼠给药后第2、4、6、8周血清代谢表达谱的动态变化，比较不同时间的大鼠血清潜在生物标志物含量变化，依据代谢通路分析构建药物-靶点-通路网络图。结果 蒙古扁桃石油醚提取物可纠正CCl₄诱导的肝纤维化疾病发展各阶段代谢谱，实验第2周时未见其对肝纤维化早期关键生物标志物产生回调；中期（第4周）主要通过作用于胆固醇和鞘磷脂，减轻肝损伤，延缓肝纤维化形成；晚期（第8周）主要通过回调鞘氨醇、鞘磷脂、胆固醇等8个关键生物标志物水平，参与鞘脂类、甘油磷脂代谢，初级胆汁酸生物合成，缬氨酸、亮氨酸、异亮氨酸的生物合成与降解，发挥抗纤维化作用；蒙古扁桃石油醚提取物中剂量（1.25 g/kg）对代谢谱回调趋势更明显，对差异代谢物及关键生物标志物回调数量较多，抗肝纤维化效果较佳。结论 基于UPLC-MS代谢组学技术从微观代谢角度揭示了蒙古扁桃石油醚提取物可通过多靶点影响肝纤维化代谢物水平及其相关代谢通路，从而有效改善肝纤维化。

Objective Serum metabolomics were utilized to explore the effects of the petroleum ether extract of Amygdala mongolica on the metabolic profile and biomarkers in hepatic fibrosis progression, and to clarify its mechanisms of anti-HF from the perspective of metabolism. Methods Rats were sc carbon tetrachloride (CCl₄) for 8 weeks to establish liver fibrosis model, and ig petroleum ether extract of A. mongolica (1.75, 1.25, 0.75 g/kg) and silymarin (50 mg/kg). Serum metabolic profiling was performed by UPLC-Q-TOF/MS to explore the dynamic changes of metabolic spectrum in all experimental groups at weeks 2, 4, 6, and 8. The serum potential and dynamical biomarkers alteration in each group during different time points were compared. The drug-target-pathway network was constructed by metabolic pathway analysis. Results The petroleum ether extract of A. mongolica restored the CCl₄-induced alteration of metabolic spectrum in all stages of hepatic fibrosis. However, there was no effect on the key biomarkers in the early stage of liver fibrosis at the week 2 after being treated with A. mongolica, while it could reduce liver injury and mitigate the development of liver fibrosis by regulating cholesterol and sphingomyelin in the middle stage (4 weeks). In the late stage (8 weeks), A. mongolica played an anti-fibrosis role by reversing eight key biomarkers including sphingosine, sphingomyelin and cholesterol, participating in sphingomyelin metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis; And participating in biosynthesis and degradation of valine, leucine, isoleucine. In addition, the petroleum ether extract of A. mongolica (1.25 g/kg) group had better efficacies due to more obvious tendency for the callback of metabolic spectrum, and more restored differential metabolites and key biomarkers. Conclusion UPLC-MS-based metabonomic analysis revealed that petroleum ether extract of A. mongolica can effectively improve hepatic fibrosis through multi-target effect on hepatic fibrosis metabolites and related metabolic pathways

国家自然科学基金资助项目（81760782）；国家自然科学基金资助项目（81641137）；内蒙古自然科学基金资助项目（2017MS0813）；内蒙古自然科学基金资助项目（2018LH03027）；内蒙古自治区“草原英才”工程青年创新创业一层次人才项目（Q2017046）；包头医学院博士科研启动基金资助项目（BSJJ201809）；北京中医药大学新教师启动基金资助项目（2019-JYB-XJSJJ-023）