六味地黄丸对大鼠生长发育过程中血液代谢的影响  

Effect of Liuwei Dihuangwan on Blood Metabolism During Growth and Development of Rats

作　　者：康舒宇 张艾嘉 张佳琪 王萍 王喜军 KANG Shu-yu;ZHANG Ai-jia;ZHANG Jia-qi;WANG Ping;WANG Xi-jun(Sino-America Chinmedomics Technology Collaboration Center, Key Laboratory of Serum Pharmacochemistry, Research Center of Chinmedomics, State Administration of Traditional Chinese Medicine (TCM), Heilongjiang University of Chinese Medicine, Harbin 150040 , China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700,China)

机构地区：[1]黑龙江中医药大学国家中医药管理局中医方证代谢组学研究中心国家中医药管理局中药血清药物化学重点研究室中美中医方证代谢组学技术合作中心,哈尔滨150040 [2]中国中医科学院中药研究所,北京100700

出　　处：《中国实验方剂学杂志》2019年第12期1-8,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81473584)

摘　　要：目的:以代谢组学的整体代谢轮廓和生物标记物为指标,研究六味地黄丸对大鼠生长发育过程中血液代谢的影响。方法:利用超高效液相色谱-高清质谱(UPLC-HDMS)联用技术建立血液代谢组学研究方法,表征给药前后不同时间的大鼠血液代谢轮廓;采用模式识别方法整合分析代谢轮廓,寻找与药物作用相关的差异代谢标记物,依托MetPA和京都基因与基因组百科全书(KEGG)等数据库,解析与差异标记物相关的代谢通路,研究六味地黄丸对大鼠生长发育过程中血液代谢的影响。结果:六味地黄丸通过调控苯丙氨酸、酪氨酸、亮氨酸、硫酸高香草酸、溶血性磷脂酰胆碱[16∶1(9Z)]等30个血液代谢标记物及12个相关的靶标代谢通路,显著影响大鼠生长发育过程中血液代谢轮廓,并圈定了硫酸高香草酸、苯丙氨酸、甘氨胆酸等8个代谢标记物为六味地黄丸影响大鼠生长发育的核心代谢标记物。结论:六味地黄丸能够显著调控大鼠生长发育过程中的血液代谢网络,从而影响大鼠的生长发育。Objective: The effect of Liuwei Dihuangwan on blood metabolism during growth and development of rats was investigated by taking the overall metabolic profile and biomarkers of metabolomics as indexes. Method: Ultra performance liquid chromatography-high definition mass spectrometry( UPLC-HDMS)was employed to establish a blood metabolomics study method for characterizing the blood metabolic profile of rats at different time before and after administration. The pattern recognition method was used to integrate and analyze the metabolic profiles, and the differential metabolic markers related to drug action were searched. Based on metabolomics pathway analysis( MetPA) and Kyoto encyclopedia of genes and genomes( KEGG) and other databases,the metabolic pathways related to differential markers were analyzed to study the effect of Liuwei Dihuangwan on blood metabolism during growth and development of rats. Result: Liuwei Dihuangwan significantly affect the blood metabolism profiles during growth and development of rats by regulating 30 blood metabolic markers and 12 related target metabolic pathways,and 8 key metabolic markers were delineated. Conclusion: Liuwei Dihuangwan can significantly regulate the blood metabolic network during the growth and development of rats,thereby affecting the growth and development of rats.

关 键 词：六味地黄丸 生长发育 血液代谢 代谢标记物 氨基酸代谢 硫酸高香草酸 甘氨胆酸 

分 类 号：R22[医药卫生—中医基础理论] R24[医药卫生—中医学]