基于代谢组学的儿童支气管哮喘急性发作期证候学生物标记物研究

The bronchial asthma is a kind of common and frequently-occurring disease that affects the children's health and growth. At present, Chinese medical syndrome differentiation of the bronchial asthma in children has well established by clinical. However, the biological basis of each syndrome remains unclear. In this study, Liquid Chromatography-Mass Spectrometry(LC-MS), Gas Chromatography-Mass Spectrometry(GC-MS), integrating with chemometric analysis techniques are applied to explore the TCM syndrome of the bronchial asthma in children with the purpose of quantitative characterization and standardized diagnosis. Firstly, plasma, urine and exhaled breath condensate samples of clinicians are analyzed by LC-MC and GC-MS TO describe the distinctive metabolic profiles of four different syndromes, including wind-cold fettering in the lung, phlegm-heat stagnating in the lung, cold-outside and heat-inside, and lung-excess and kidney deficiency. Then, the biomarker extraction are analyzed based on the multivariant analysis. Finally, by metabolic network construction, the scientific essence of syndrome is demonstrated. The results of this project will guide the clinical diagnosis, provide the relationship of syndrome and disease, and reveal the potential mechanisms of each syndrome. The finding are expected to give insights into scientific essence of the bronchial asthma.

儿童支气管哮喘是小儿常见病和多发病，对小儿生长发育有着重要影响。为实现儿童支气管哮喘急性发作期证候客观量化表征，促进其临床诊断、辨证的规范化和标准化，本项目拟采用液质联用技术（LC-MS）、气质联用技术（GC-MS）和化学计量学分析研究技术，从整体上研究儿童支气管哮喘疾病及其主要证候的代谢组学特征和规律。通过研究支气管哮喘急性发作期患儿血液、尿液和呼气冷凝液中代谢网络的变化特征，建立基于生物标记物表达差异的风寒束肺证、痰热阻肺证、外寒内热证、肺实肾虚证的特征谱库，分析代谢网络的变化并寻找最佳生物标记物，同时结合分子生物学技术揭示儿童支气管哮喘急性发作期证候的科学实质。通过本项研究，可进一步明确儿童支气管哮喘急性发作期证候辨证依据、揭示病证关系、探讨生物学基础，进一步总结临床辨证经验，研究证候客观量化表征，为创新临床适用的儿童支气管哮喘急性发作期辨证论治体系提供理论基础。

儿童支气管哮喘是一种以慢性气道炎症为特征的异质性疾病，以反复发作的喘息、气促、胸闷、咳嗽、可逆性气流受限为临床表现，由于反复发作，严重影响患儿的生长发育与生活质量，也给患儿家长带了极大的精神压力。中医药在治疗该病方面具有显著优势，但中医辨识哮喘缺乏客观诊断依据与指标。本研究采用液相-质谱联用技术（LC-MS）检测儿童支气管患儿血液、尿液、呼吸冷凝液中的相关代谢产物，建立了基于生物标志物表达差异的风寒束肺证、痰热阻肺证、外寒内热证、肺实肾虚证的特征代谢谱库，发现了哮喘患儿大量代谢物质发生变化，主要集中在精氨酸代谢、组氨酸代谢、苯丙氨酸代谢、半乳糖代谢、磷酸戊糖代谢、淀粉和蔗糖代谢、花生四烯酸代谢、鞘脂代谢等途径中的物质，推测这些代谢通路可能在儿童哮喘发生发展过程中发挥了重要作用，为进一步研究不同证候特征性生物标志物，并将其运用于临床诊断奠定了基础。