六味地黄丸对大鼠生长发育过程中血液代谢的影响
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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.
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.
引文
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[13]李秋菊,王萍,王美佳,等.基于中医方证代谢组学技术的六味地黄丸干预脑瘫大鼠模型研究[J].世界科学技术—中医药现代化,2016,18(10):1684-1696.
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[15]王喜军,张宁,孙晖,等.六味地黄丸血中移行成分对氢化可的松致大鼠肾虚动物模型的保护作用[J].中国实验方剂学杂志,2008,14(2):33-37.
[16]杜亚明,李祥华,张家均.六味地黄丸对2型糖尿病大鼠胰岛素抵抗的影响[J].中药药理与临床,2012,28(6):6-9.
[17]ZHANG Y X,MA Y,ZHOU W,et al. Effect of Liuwei Dihuang decoction on the function of hypothalamuspituitary-ovary axis in senescence-accelerated mouse[J]. Chin J Integr Tradit Chin West Med,2004,24(4):325-330.
[18]LIU J P,FENG L,ZHANG M H,et al. Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat[J]. J Ethnopharmacol,2013,150(1):371-381.
[19]ZHOU W X,CHENG X R,ZHANG Y X. Effect of Liuwei Dihuang decoction, a traditional Chinese medicinal prescription, on the neuroendocrine immunomodulation network[J]. Pharmacol Ther,2016,162:170-178.
[20]WANG J,YAO K W,YANG X C,et al. Chinese patent medicine Liu Wei Di Huang Wan combined with antihypertensive drugs, a new integrative medicine therapy,for the treatment of essential hypertension:a systematic review of randomized controlled trials[J].Evid Based Complement Alternat Med,2012,doi:10. 1155/2012/714805.
[21]Stonier C,McGale E H,Aber G M. Studies of phenylalanine hydroxylase activity in patients with chronic renal failure:the effect of haemodialysis[J]. Clin Chim Acta,1984,143(2):115-122.
[22]Rasmussen D D,Ishizuka B,Quigley M E,et al. Effects of tyrosine and tryptophan ingestion on plasma catecholamine and 3,4-dihydroxyphenylacetic acid concentrations[J]. J Clin Endocrinol Metab,1983,57(4):760-763.
[23]张将,唐爱国.色氨酸及其代谢产物检测的临床应用[J].实用预防医学,2012,19(4):633-636.
[24]陈浩,毛湘冰,陈代文,等.亮氨酸调节哺乳动物脂肪代谢的研究进展[J].动物营养学报,2014,26(7):1723-1727.
[25]康舒宇,张佳琪,张艾嘉,等.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.
[2]张贤锋.实用儿科疾病诊断与治疗[M].延吉:延边大学出版社,2017:3.
[3]郑洪新.中医基础理论[M].北京:中国中医药出版社,2016:59-61.
[4]王萍,王喜军.六味地黄丸研究现状[J].中医药信息,2013,30(3):163-165.
[5]Goodacre R,Vaidyanathan S,Dunn W B,et al.Metabolomics by numbers:acquiring and understanding global metabolite data[J]. Trends Biotechnol,2004,22(5):245-252.
[6]ZHANG A H,SUN H,WANG Z G,et al. Metabolomics:towards understanding traditional Chinese medicine[J].Planta Med,2010,76(17):2026-2035.
[7]郝明丽,徐敏.代谢组学在2型糖尿病研究中的应用及进展[J].内科理论与实践,2016,11(3):191-194.
[8]TIAN J S,XIA X T,WU Y F,et al. Discovery,screening and evaluation of a plasma biomarker panel for subjects with psychological suboptimal health state using1HNMR-based metabolomics profiles[J]. Sci Rep,2016,6:33820.
[9]XIE J,ZHANG A H,WANG X J. Metabolomic applications in hepatocellular carcinoma:toward the exploration of therapeutics and diagnosis through small molecules[J]. RSC Adv,2017,7(28):17217-17226.
[10]陈瑞,马宁宁,范姗姗,等.基于代谢组学分析金芪降糖片改善2型糖尿病大鼠脂代谢紊乱的作用机制[J].中国实验方剂学杂志,2018,24(20):102-107.
[11]王喜军.中药药效物质基础研究的系统方法学——中医方证代谢组学[J].中国中药杂志,2015,40(1):13-17.
[12]WANG X J,ZHANG A H,SUN H. Future perspectives of Chinese medical formulae:chinmedomics as an effector[J]. Omics,2012,16(7/8):414-421.
[13]李秋菊,王萍,王美佳,等.基于中医方证代谢组学技术的六味地黄丸干预脑瘫大鼠模型研究[J].世界科学技术—中医药现代化,2016,18(10):1684-1696.
[14]WANG P,SUN H,LV H T,et al. Thyroxine and reserpine-induced changes in metabolic profiles of rat urine and the therapeutic effect of Liu Wei Di Huang Wan detected by UPLC-HDMS[J]. J Pharm Biomed Anal,2010,53(3):631-645.
[15]王喜军,张宁,孙晖,等.六味地黄丸血中移行成分对氢化可的松致大鼠肾虚动物模型的保护作用[J].中国实验方剂学杂志,2008,14(2):33-37.
[16]杜亚明,李祥华,张家均.六味地黄丸对2型糖尿病大鼠胰岛素抵抗的影响[J].中药药理与临床,2012,28(6):6-9.
[17]ZHANG Y X,MA Y,ZHOU W,et al. Effect of Liuwei Dihuang decoction on the function of hypothalamuspituitary-ovary axis in senescence-accelerated mouse[J]. Chin J Integr Tradit Chin West Med,2004,24(4):325-330.
[18]LIU J P,FENG L,ZHANG M H,et al. Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat[J]. J Ethnopharmacol,2013,150(1):371-381.
[19]ZHOU W X,CHENG X R,ZHANG Y X. Effect of Liuwei Dihuang decoction, a traditional Chinese medicinal prescription, on the neuroendocrine immunomodulation network[J]. Pharmacol Ther,2016,162:170-178.
[20]WANG J,YAO K W,YANG X C,et al. Chinese patent medicine Liu Wei Di Huang Wan combined with antihypertensive drugs, a new integrative medicine therapy,for the treatment of essential hypertension:a systematic review of randomized controlled trials[J].Evid Based Complement Alternat Med,2012,doi:10. 1155/2012/714805.
[21]Stonier C,McGale E H,Aber G M. Studies of phenylalanine hydroxylase activity in patients with chronic renal failure:the effect of haemodialysis[J]. Clin Chim Acta,1984,143(2):115-122.
[22]Rasmussen D D,Ishizuka B,Quigley M E,et al. Effects of tyrosine and tryptophan ingestion on plasma catecholamine and 3,4-dihydroxyphenylacetic acid concentrations[J]. J Clin Endocrinol Metab,1983,57(4):760-763.
[23]张将,唐爱国.色氨酸及其代谢产物检测的临床应用[J].实用预防医学,2012,19(4):633-636.
[24]陈浩,毛湘冰,陈代文,等.亮氨酸调节哺乳动物脂肪代谢的研究进展[J].动物营养学报,2014,26(7):1723-1727.
[25]康舒宇,张佳琪,张艾嘉,等.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.
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