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基于血清代谢组学策略解析肾气丸对肾阳虚证药理作用

Serum metabolomics strategy for understanding pharmacological effects of ShenQi pill acting on kidney yang deficiency syndrome.

作者信息

Nan Yang, Zhou Xiaohang, Liu Qi, Zhang Aihua, Guan Yu, Lin Shanhua, Kong Ling, Han Ying, Wang Xijun

机构信息

National TCM Key Lab of Serum Pharmacochemistry, Key Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.

National TCM Key Lab of Serum Pharmacochemistry, Key Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jul 15;1026:217-226. doi: 10.1016/j.jchromb.2015.12.004. Epub 2015 Dec 19.

Abstract

Kidney yang deficiency syndrome, a diagnostic pattern in Chinese medicine, is similar with clinical features of the glucocorticoid withdrawal syndrome. The aim of this present study was to explore low molecular mass differentiating metabolites between control group and model group of kidney yang deficiency rats induced with corticosterone as well as the therapeutic effect of Shen Qi Pill, a classic traditional Chinese medicine formula for treating Kidney yang deficiency syndrome in China. This study utilized ultra-performance liquid chromatography coupled with electrospray ionization synapt quadrupole time-of-flight high definition mass spectrometry (UPLC/ESI-SYNAPT-QTOF-HDMS) to identify the underlying biomarkers for clarifying mechanism of Shen Qi Pill in treating Kidney yang deficiency syndrome based on metabolite profiling of the serum samples and in conjunction with multivariate and pathway analysis. Meanwhile, blood biochemistry assay and histopathology were examined to identify specific changes in the model group rats. Distinct changes in the pattern of metabolites were observed by UPLC-HDMS. The changes in metabolic profiling were restored to their baseline values after treatment with Shen Qi Pill according to the combined with a principal component analysis (PCA) score plots. Altogether, the current metabolomics approach based on UPLC-HDMS and orthogonal projection to latent structures discriminate analysis (OPLS-DA) demonstrated 27 ions (18 in the negative mode, 9 in the positive mode, 17 ions restored by Shen Qi Pill). These results indicated that effectiveness of Shen Qi Pill in Kidney yang deficiency syndrome rats induced a substantial change in the metabolic profiles by regulating the biomarkers and adjusting the metabolic disorder. It suggested that the metabolomics approach was a powerful approach for elucidation of pathologic changes of Chinese medicine syndrome and action mechanisms of traditional Chinese medicine.

摘要

肾阳虚证是中医的一种诊断模式,与糖皮质激素撤药综合征的临床特征相似。本研究的目的是探索以皮质酮诱导的肾阳虚大鼠对照组与模型组之间的低分子量差异代谢物,以及中国治疗肾阳虚证的经典中药方剂肾气丸的治疗效果。本研究利用超高效液相色谱联用电喷雾电离串联四极杆飞行时间高清质谱(UPLC/ESI-SYNAPT-QTOF-HDMS),基于血清样本的代谢物谱分析,并结合多变量和通路分析,识别潜在生物标志物,以阐明肾气丸治疗肾阳虚证的机制。同时,检测血液生化指标和组织病理学,以确定模型组大鼠的具体变化。通过UPLC-HDMS观察到代谢物模式有明显变化。根据主成分分析(PCA)得分图,用肾气丸治疗后,代谢谱变化恢复到基线值。总之,基于UPLC-HDMS和正交投影到潜在结构判别分析(OPLS-DA)的当前代谢组学方法显示出27种离子(负模式下18种,正模式下9种,17种离子经肾气丸恢复)。这些结果表明,肾气丸对肾阳虚证大鼠的有效性通过调节生物标志物和调整代谢紊乱,使代谢谱发生了实质性变化。这表明代谢组学方法是阐明中医证候病理变化和中药作用机制的有力方法。

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