目的 系统评价当归六黄汤（Danggui Liuhuang Decoction，DGLHD）对甲状腺功能亢进症（甲亢）的干预作用，发现相关药效物质基础，阐明其作用机制，为DGLHD的后续开发提供科学依据。方法 采用左甲状腺素钠制备甲亢大鼠模型，运用方证代谢组学策略，表征甲亢模型的代谢轮廓及生物标记物；以经典药理学相关参数为指标，评价DGLHD对甲亢的干预作用，在有效状态下分析DGLHD的血中移行成分，利用中医方证代谢组学研究中心（Pearson Correlation between Marker Metabolites and Serum Constituents，PCMS）方法挖掘DGLHD血中移行成分与模型生物标记物关联度，揭示DGLHD干预甲亢的药效物质基础。结果 DGLHD对甲亢模型大鼠的体质量、心率、肛温、进食量及呼吸商等指标异常具有调节作用；对生化指标三碘甲状腺原氨酸、甲状腺素、游离三碘甲状腺原氨酸、游离甲状腺素、促甲状腺激素可显著回调；其改变甲亢大鼠的血液代谢轨迹，回调1H-吲哚-3-甲醛等18个标记物的紊乱表达；主要通过调节甘油磷脂代谢、初级胆汁酸生物合成、类固醇激素生物合成等代谢通路抑制炎症因子表达，发挥免疫调节作用。在DGLHD干预大鼠的血清中，表征了46个血中移行成分，其中38个成分与甲亢血液代谢生物标记物具有相关性，其中洋川芎内酯I等13个成分为与干预作用高度相关的关键药效物质基础。结论 DGLHD中洋川芎内酯I等成分通过调节甘油磷脂代谢等代谢网络紊乱，发挥抑制炎症因子、改善新陈代谢、调节免疫功能的作用，为DGLHD质量标准的建立及基于药效物质基础的新药创制提供科学依据。

Objective To systematically evaluate the interventional effect of Danggui Liuhuang Decoction (当归六黄汤, DGLHD) on hyperthyroidism, discover the relevant pharmacodynamic material basis, and elucidate its mechanism of action, thereby providing scientific evidence for the subsequent development of DGLHD. Methods A hyperthyroidism rat model was prepared by using levothyroxine sodium, and the metabolic profile and biomarkers of the hyperthyroidism model were characterized by chinmedomics; the interventional effect of DGLHD on hyperthyroidism was evaluated by using the classical pharmacological parameters of the model as the indexes, and the blood migratory constituents of DGLHD were analyzed under the effective state, and the correlation between the blood migratory constituents of DGLHD and the biomarkers of the model was explored by Pearson Correlation between Marker Metabolites and Serum Constituents (PCMS) method to reveal the pharmacodynamic material basis of DGLHD intervention in hyperthyroidism. Results DGLHD had a modulating effect on the abnormalities of body weight, heart rate, anal temperature, food intake and respiratory quotient of hyperthyroidism model rats; it significantly regulated the biochemical indexes of triiodothyronine, thyroxine, free triiodothyronine, free thyroxine and thyroid-stimulating hormone; it altered the metabolic trajectory of the blood in the hyperthyroidism model rats, and regulated the disturbed expression of 18 markers such as 1H-indole-3-carboxaldehyde. It inhibited the expression of inflammatory factors and played the role of immunomodulation by regulating the metabolic pathways such as glycerophospholipid metabolism, primary bile acid biosynthesis and steroid hormone biosynthesis. In the serum of rats treated with DGLHD, a total of 46 blood components were characterized, of which 38 were correlated with the blood metabolic biomarkers of hyperthyroidism, with 13 components, including senkyunolide I, identified as critical pharmacodynamic substances demonstrating high relevance to the therapeutic intervention. Conclusion It is found that components such as senkyunolide I in DGLHD could inhibit inflammatory factors, improve metabolism, and regulate immune function by regulating metabolic network disorders such as glycerophospholipid metabolism. This study provides a scientific basis for the establishment of the quality standard of DGLHD and the creation of new drugs based on thepharmacodynamic material basis.

R285

黑龙江中医药大学科研基金项目（201809）