National TCM Key Lab of Serum Pharmacochemistry, Key Laboratory of Chinmedomics and Metabolomics, Heilongjiang University of Chinese Medicine, and Key Pharmacometabolomics Platform of Chinese Medicines, Harbin 150040, China.
National TCM Key Lab of Serum Pharmacochemistry, Key Laboratory of Chinmedomics and Metabolomics, Heilongjiang University of Chinese Medicine, and Key Pharmacometabolomics Platform of Chinese Medicines, Harbin 150040, China.
Chin J Nat Med. 2013 Nov;11(6):653-65. doi: 10.1016/S1875-5364(13)60076-X.
Metabolomics represents an emerging and powerful discipline that provides an accurate and dynamic picture of the phenotype of bio-systems through the study of potential metabolites that could be used as therapeutic targets and for the discovery of new drugs. Hepatitis C virus (HCV) is a leading cause of liver disease worldwide, and is a major burden on public health. It is hypothesized that an animal model of HCV infection would produce unique patterns of endogenous metabolites. Herein, a method for the construction of efficient networks is presented with regard to the proteins of bear bile powder (PBBP) that protect against HCV as a case study. Ultra-performance liquid chromatography, coupled with electrospray ionization/quadrupole-time-of-flight high definition mass spectrometry (UPLC-HDMS), coupled with pattern recognition methods and computational systems analysis were integrated to obtain comprehensive metabolomic profiling and pathways of the large biological data sets. Among the regulated pathways, 38 biomarkers were identified and two unique metabolic pathways were indicated to be differentially affected in HCV animals. The results provided a systematic view of the development and progression of HCV, and also could be used to analyze the therapeutic effects of PBBP, a widely used anti-HCV medicine. The results also showed that PBBP could provide satisfactory effects on HCV infection through partially regulating the perturbed pathway. The most promising use in the near future would be to clarify the pathways for the drugs and obtain biomarkers for these pathways to help guide testable predictions, provide insights into drug action mechanisms, and enable an increase in research productivity toward metabolomic drug discovery.
代谢组学代表了一个新兴的、强大的学科，它通过研究可能作为治疗靶点和新药发现的潜在代谢物，为生物系统的表型提供了一个准确和动态的描述。丙型肝炎病毒（HCV）是全球范围内导致肝脏疾病的主要原因，也是公共卫生的主要负担。据推测，HCV 感染的动物模型将产生独特的内源性代谢物模式。本文以熊去氧胆酸（UDCA）蛋白防治 HCV 感染为例，提出了一种构建高效网络的方法。采用超高效液相色谱-电喷雾电离/四极杆飞行时间高分辨质谱（UPLC-HDMS），结合模式识别方法和计算系统分析，对大生物数据集进行全面代谢组学分析和途径分析。在所调节的途径中，鉴定出 38 个生物标志物，并指出 HCV 动物中两个独特的代谢途径受到差异影响。研究结果提供了 HCV 发展和进展的系统观点，也可用于分析熊去氧胆酸（UDCA）这一广泛应用的抗 HCV 药物的治疗效果。结果还表明，熊去氧胆酸（UDCA）可以通过部分调节失调途径对 HCV 感染提供满意的效果。在不久的将来，最有希望的用途是阐明药物的途径，并获得这些途径的生物标志物，以帮助指导可测试的预测，深入了解药物作用机制，并提高代谢组学药物发现的研究生产力。
