目的：本研究基于中医方证代谢组学理论和技术平台，研究六味地黄丸（LW）对脑瘫大鼠模型的干预作用。方法：研究采用延迟剖宫产手术方法复制缺氧缺血脑瘫（HICP）大鼠模型，利用经典行为学方法对HICP模型和LW的干预作用进行评价；最后借助中医方证代谢组学技术揭示了HICP模型大鼠尿液的潜在生物标记物与LW干预HICP模型体内显效成分的相关性。结果：研究表明LW通过调节HICP模型大鼠机体的糖类代谢、氨基酸代谢、核苷酸代谢和甾体激素类生物合成四大类代谢途径，进而有效改善HICP模型大鼠的运动能力，并确定LW的入血成分中6-O-甲基梓醇、莫诺苷、丹皮酚原苷、毛蕊花苷、獐牙菜苷脱水的代谢产物为干预HICP大鼠模型的潜在药效物质基础。本证实了中医方证代谢组学技术可以成为阐明中药药效物质基础的有力手段。

This study aimed to explore the pharmacodynamic material basis of Liu Wei Di Huang Wan(LW)in the rat model of cerebral palsy and its mechanism based on the theory and technological platform of Chinmedomics.The delayed cesarean operation was performed to establish the rat model of hypoxic-ischemic cerebral palsy(HICP)and ensued the evaluation of the model with classical behavior and the administration of LW.At last,the correlation between the potential biomarkers of HICP was computed and the markedly component of LW in vivo was explored by the technologies of chinmedomics.It was found that four categories of metabolic pathways of HICP rats were regulate within the administration of LW,involving carbohydrate metabolism,amino acid metabolism,nucleotide metabolism and steroid hormone synthesis biological metabolic,to promote motor ability of HICP rats.It was determined that 6-O-methylcatalpol,morroniside,verbascose,paeonolide,and the dehydrated metabolite of Sweroside were the potential pharmacodynamic materials of LW in its treatment of HICP.It was concluded that chinmedomics was a powerful method of clarifing the pharmacodynamic materials of Chinese materia medica.

国家自然科学基金委重点项目（81430093）：中药体内药效物质基础的系统分析方法学——中医方证代谢组学研究，负责人：王喜军；科学技术部“重大新药创制”国家科技重大专项（2015ZX09101043-011）：课题名称：中药经典名方整合作用机制关键技术研究，负责人：王喜军；国家自然科学基金委面上项目（81473584）：基于新生大鼠脑瘫模型的六味地黄丸治疗“五迟”、“五软”证的作用机理及药效物质基础研究，负责人：王萍。