药学学报, 2018, 53(10): 1713-1720
引用本文:
康舒宇, 张佳琪, 张艾嘉, 王萍, 王喜军. 基于尿液代谢组学的六味地黄丸对大鼠生长发育的影响[J]. 药学学报, 2018, 53(10): 1713-1720.
KANG Shu-yu, ZHANG Jia-qi, ZHANG Ai-jia, WANG Ping, WANG Xi-jun. Based on urine metabolomics to study effect of Liuwei Dihuang Wan on growth and development of rats[J]. Acta Pharmaceutica Sinica, 2018, 53(10): 1713-1720.

基于尿液代谢组学的六味地黄丸对大鼠生长发育的影响
康舒宇1, 张佳琪1, 张艾嘉1, 王萍1,2, 王喜军1
1. 黑龙江中医药大学, 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实验室, 中美中医方证代谢组学技术合作中心, 黑龙江 哈尔滨 150040;
2. 中国中医科学院中药研究所, 北京 100700
摘要:
构建以传统的生理研究为基础,以尿液代谢组学的整体代谢轮廓和生物标记物为指标的六味地黄丸(LW)调控大鼠生长发育的综合药效评价体系。将27日龄SD大鼠60只随机分为对照组、六味地黄丸低、中、高剂量组,28日龄开始连续灌胃给予不同剂量的六味地黄丸提取液16天。在行为学、体重、脏器指数及股骨长度的基础上,应用UPLC-HDMS联用技术建立尿液代谢组学研究方法,表征六味地黄丸干预前后的尿液代谢轮廓,分析鉴定与药物作用相关的差异代谢标记物,研究六味地黄丸对大鼠生长发育的影响。结果表明,六味地黄丸能够提升大鼠的整体行为能力,促进体重增长及脏器和骨骼生长,确定了六味地黄丸干预下的尿液差异代谢标记物36个及靶标代谢通路13个,圈定了8个代谢标记物作为六味地黄丸影响大鼠生长发育的关键标记物。研究阐明了六味地黄丸对大鼠生长发育过程中尿液代谢网络具有显著的调控作用,诠释了“滋补肾阴”对大鼠生长发育影响的科学内涵。
关键词:    六味地黄丸      生长发育      代谢组学     
Based on urine metabolomics to study effect of Liuwei Dihuang Wan on growth and development of rats
KANG Shu-yu1, ZHANG Jia-qi1, ZHANG Ai-jia1, WANG Ping1,2, WANG Xi-jun1
1. Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Laboratory of Metabolomics, Heilongjiang University of Chinese Medicine, Harbin 150040, China;
2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Abstract:
On base of traditional physiological studies, building a comprehensive evaluation system for the efficacy of Liuwei Dihuang Wan (LW) for regulating the growth and development of rats by indicators that the overall metabolic profile and biomarkers of urinary metabonomics. Sixty-seven day-old Sprague-Dawley rats were randomly divided into four groups that are the control group and low-dose, medium-dose, and high-dose groups of LW. At the age of 28 days, different doses of LW extracts were continuously administered for 16 days. On the basis of behavior, body weight, organ index and femur length, a UPLC-HDMS technique was used to establish urine metabolomics method to characterize the profile of urine metabolism before and after intervention of LW, analysis and identificate related to drug effects of differential metabolism markers, and study the effect of LW on the growth and development of rats. LW could improve the overall behavioral ability of rats, promote weight gain and the growth of organs and bones, and 36 differential metabolites and 13 target metabolic pathways of urine under the intervention of LW were identified, and 8 metabolic markers were regarded as a key marker that LW effect the growth and development of rats. LW has a significant regulatory effect on the urine metabolic network during the growth and development of rats. This study interpreted the scientific implications of the effect of "Nourishing Kidney Yin" on the growth and development of rats.
Key words:    Liuwei Dihuang Wan    the growth and development    metabolomics   
收稿日期: 2018-05-14
DOI: 10.16438/j.0513-4870.2018-0446
基金项目: 国家自然科学基金面上项目(81473584).
通讯作者: 王萍,Tel:86-10-64032656,Fax:86-10-64013996,E-mail:hudielanwp@sina.com;王喜军,Tel/Fax:86-451-82110818,E-mail:xijunw@sina.com
Email: hudielanwp@sina.com;xijunw@sina.com
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