目的 观察甘草炮制雷公藤Tripterygium wilfordii后对小鼠血清中代谢产物的影响，初步探讨其降低肝毒性的可能代谢通路。方法 将C57BL/6小鼠随机分为对照（Con）组、雷公藤（Raw）组、甘草炮制雷公藤（Pro）组，观察小鼠肝组织病理变化，检测小鼠肝功能生化指标、炎症因子水平；利用液质联用（LC-MS）技术结合代谢组学方法，对各组间的代谢差异进行表征。结果 与Raw组相比，Pro组小鼠肝组织损伤显著改善，肝功能生化指标、炎症因子水平显著降低，表明甘草炮制雷公藤后可以降低小鼠肝毒性；共筛选出脂肪酸、磷脂酸、甘油酯、磷脂酰胆碱、胆酸等12个潜在生物标志物，主要涉及脂肪酸生物合成、甘油磷脂代谢、花生四烯酸代谢等9个代谢通路。结论 甘草炮制雷公藤可有效降低小鼠的肝毒性，其机制可能与调节脂肪酸代谢等通路相关，为其临床合理应用提供参考依据。

Objective To observe the effect of Tripterygium wilfordii processed by liquorice on the metabolites in the serum of mice, and to explore its possible metabolic pathways to reduce hepatotoxicity. Methods C57BL/6 mice were randomly divided into control (Con) group, raw T. wilfordii (Raw) group, and T. wilfordii processed by liquorice (Pro) group. Liver histopathological sections and biochemical indexes of liver function and inflammatory factors were detected. LC-MS technology combined with metabolomics methods were used to characterize the differences in metabolism between each group. Results Compared with Raw group, the liver injury of mice in Pro group was significantly improved, the levels of biochemical indicators and inflammatory factors were significantly decreased, which indicated that TwHF could reduce the hepatotoxicity of mice after processing by liquorice. Twelve potential biomarkers including hexadecanoic acid, phosphatidic acid, glyceride, lecithin and cholic acid were screened, mainly involved nine metabolic pathways including biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, arachidonic acid metabolism, etc. Conclusion TwHF processed by liquorice could reduce the hepatotoxicity of mice and the mechanism may be related to the regulation of fatty acid metabolism, which provides a reference for clinical rational application.

R285.53

首都卫生发展科研专项项目（首发2016-4-2024）；北京市中医药科技项目（QN2014-18）；首都医科大学附属北京友谊医院“种子计划”项目（YYZZ2018A02）