Zhang Aihua, Zhou Xiaohang, Zhao Hongwei, Zou Shiyu, Ma Chung Wah, Liu Qi, Sun Hui, Liu Liang, Wang Xijun
Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
Infinitus (China) Company Ltd, Guangzhou, China.
Mol Biosyst. 2017 Jan 31;13(2):320-329. doi: 10.1039/c6mb00677a.
An integrative metabolomics and proteomics approach can provide novel insights in the understanding of biological systems. We have integrated proteome and metabolome data sets for a holistic view of the molecular mechanisms in disease. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UPLC-Q-TOF-HDMS based metabolomics, we determined the protein and metabolite expression changes in the kidney-yang deficiency syndrome (KYDS) rat model and further investigated the intervention effects of the Jinkui Shenqi Pill (JSP). The VIP-plot of the orthogonal PLS-DA (OPLS-DA) was used for discovering the potential biomarkers to clarify the therapeutic mechanisms of JSP in treating KYDS. The results showed that JSP can alleviate the kidney impairment induced by KYDS. Sixty potential biomarkers, including 5-l-glutamyl-taurine, phenylacetaldehyde, 4,6-dihydroxyquinoline, and xanthurenic acid etc., were definitely up- or down-regulated. The regulatory effect of JSP on the disturbed metabolic pathways was proved by the established metabonomic method. Using pathway analyses, we identified the disturbed metabolic pathways such as taurine and hypotaurine metabolism, pyrimidine metabolism, tyrosine metabolism, tryptophan metabolism, histidine metabolism, steroid hormone biosynthesis, etc. Furthermore, using iTRAQ-based quantitative proteomics analysis, seventeen differential proteins were identified and significantly altered by the JSP treatment. These proteins appear to be involved in Wnt, chemokine, PPAR, and MAPK signaling pathways, etc. Functional pathway analysis revealed that most of the proteins were found to play a key role in the regulation of metabolism pathways. Bioinformatics analysis with the IPA software found that these differentially-expressed moleculars had a strong correlation with the α-adrenergic signaling, FGF signaling, etc. Our data indicate that high-throughput metabolomics and proteomics can provide an insight on the herbal preparations affecting the metabolic disorders using high resolution mass spectrometry.
整合代谢组学和蛋白质组学方法可为理解生物系统提供新的见解。我们整合了蛋白质组和代谢组数据集，以全面了解疾病中的分子机制。采用基于iTRAQ-LC-MS/MS的定量蛋白质组学技术，并结合基于UPLC-Q-TOF-HDMS的代谢组学技术，我们测定了肾阳虚证（KYDS）大鼠模型中的蛋白质和代谢物表达变化，并进一步研究了金匮肾气丸（JSP）的干预效果。利用正交偏最小二乘判别分析（OPLS-DA）的VIP图来发现潜在的生物标志物，以阐明JSP治疗KYDS的作用机制。结果表明，JSP可减轻KYDS诱导的肾脏损伤。60种潜在的生物标志物，包括5-L-谷氨酰牛磺酸、苯乙醛、4,6-二羟基喹啉和黄尿酸等，均有明显的上调或下调。通过建立的代谢组学方法证明了JSP对紊乱代谢途径的调节作用。通过通路分析，我们确定了诸如牛磺酸和次牛磺酸代谢、嘧啶代谢、酪氨酸代谢、色氨酸代谢、组氨酸代谢、类固醇激素生物合成等紊乱的代谢途径。此外，利用基于iTRAQ的定量蛋白质组学分析，鉴定出17种差异蛋白质，且JSP处理使其发生了显著变化。这些蛋白质似乎参与了Wnt、趋化因子、PPAR和MAPK信号通路等。功能通路分析表明，大多数蛋白质在代谢途径的调节中起关键作用。使用IPA软件进行的生物信息学分析发现，这些差异表达的分子与α-肾上腺素能信号、FGF信号等有很强的相关性。我们的数据表明，高通量代谢组学和蛋白质组学可以通过高分辨率质谱为影响代谢紊乱的草药制剂提供深入了解。
