Analysis of Metabolic Markers and Mechanism of Action of Youguiwan in Regulating Kidney-Yang Deficiency Syndrome by Serum Metabonomics and Support Vector Regression

CHEN Rui-qun; LIAO Cheng-bin; GUO Qian; ZHANG Lei; WANG Xiu-feng

doi:10.13422/j.cnki.syfjx.20181202

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Analysis of Metabolic Markers and Mechanism of Action of Youguiwan in Regulating Kidney-Yang Deficiency Syndrome by Serum Metabonomics and Support Vector Regression

更新时间：2024-01-04

- Analysis of Metabolic Markers and Mechanism of Action of Youguiwan in Regulating Kidney-Yang Deficiency Syndrome by Serum Metabonomics and Support Vector Regression
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 24, Issue 13, Pages: 62-70(2018)
- 作者机构：
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- DOI：10.13422/j.cnki.syfjx.20181202
  CLC： R285.5
- Published：2018
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CHEN Rui-qun, LIAO Cheng-bin, GUO Qian, et al. Analysis of Metabolic Markers and Mechanism of Action of Youguiwan in Regulating Kidney-Yang Deficiency Syndrome by Serum Metabonomics and Support Vector Regression[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(13): 62-70.
DOI：

CHEN Rui-qun, LIAO Cheng-bin, GUO Qian, et al. Analysis of Metabolic Markers and Mechanism of Action of Youguiwan in Regulating Kidney-Yang Deficiency Syndrome by Serum Metabonomics and Support Vector Regression[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(13): 62-70. DOI： 10.13422/j.cnki.syfjx.20181202.

摘要

目的：寻找右归丸（Youguiwan，YGP）治疗肾阳虚证（KYDS）的血清代谢标志物群，并进一步探索右归丸中不同药性的中药（补阳药、补阴药、补血药）对代谢标志物的调节作用。方法：利用核磁共振氢谱（1H-NMR）技术对右归丸治疗的KYDS大鼠进行血清代谢组学研究，并结合模式识别来分析血清代谢物的变化情况，从而寻找右归丸治疗KYDS的代谢标志物。同时，利用支持向量回归机（SVR）建立数学模型，分析和预测了右归丸中不同药性中药的药量变化对代谢标志物的影响，探索右归丸中不同药性的中药起调节作用的代谢物，研究右归丸的作用机制。结果：找出了22个代谢标志物，包括氨基酸代谢（亮氨酸、缬氨酸、精氨酸、丙氨酸、甲硫氨酸、谷氨酸、谷氨酰胺、苏氨酸、酪氨酸、牛磺酸），糖代谢（乳酸、乙酸和β-葡萄糖），能量代谢（甘油、肌酸、肌醇），菌群代谢[甜菜碱/氧化三甲胺（TMAO）]，脂类代谢[极低密度脂蛋白（VLDL），低密度脂蛋白（LDL）和高密度脂蛋白（HDL）]及糖蛋白[N-乙酰糖蛋白（NAG）]。SVR分析后发现补阳药主要对HDL和甜菜碱/TMAO起作用，补阴药主要对LDL/VLDL，亮氨酸和NAG起作用；补血药主要对肌酸、谷氨酸、乳酸、甲硫氨酸、肌醇和甘油起作用。结论：基于1 H-NMR的血清代谢组学能够发现肾阳虚证的代谢标志物群，与SVR结合能进一步揭示右归丸中不同药性中药调节肾阳虚证的作用机制。

Abstract

Objective: To find out the serum metabolic markers of Youguiwan (YGP) in the treatment of kidney-Yang deficiency syndrome (KYDS)

and to further explore the regulatory role of medicinal herbs (the Yang-tonifying herbs

the Yin-tonifying herbs and the blood-tonifying herbs) with different properties in YGP on the metabolic markers. Method: We used proton hydrogen nuclear magnetic resonance spectroscopy (1H-NMR) to study on the serum metabonomics of KYDS rats treated by YGP

and combined with pattern recognition to analyze the changes of serum metabolites

thereby finding the metabolic markers of YGP in the treatment of KYDS. At the same time

a mathematical model was established by support vector regression (SVR) to analyze and predict the influence of dose changes of medicinal herbs with different properties in YGP on the metabolic markers.Further exploration of which metabolites were regulated by medicinal herbs with different properties in YGP

and the mechanism of action of YGP was preliminary investigated. Result: Twenty-two metabolic markers were identified

including amino acid metabolism (leucine

valine

arginine

alanine

methionine

glutamate

glutamine

threonine

tyrosine and taurine)

glucose metabolism (lactate

acetate and β-glucose)

energy metabolism (glycerol

creatine and myo-inositol)

gut metabolism[betaine/trimetlylamine oxide (TMAO)]

lipid metabolism[very-low density lipoprotein (VLDL)

low-density lipoprotein (LDL) and high-density lipoprotein (HDL)] and glycoprotein[N-acetyl glucoside (NAG)].Furthermore

using SVR analysis and prediction

we found that the Yang-tonifying herbs mainly acted on HDL and betaine/TMAO;the Yin-tonifying herbs primarily acted on LDL/VLDL

NAG and leucine;while the blood-tonifying herbs chiefly played a role in creatine

glutamate

lactic acid

methionine

myo-inositol and glycerol. Conclusion: The serum metabonomics based on 1H-NMR can find metabolic markers of KYDS

and the mechanism of action of KYDS regulated by medicinal herbs with different properties in YGP can be further revealed by integrating with SVR.

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