急性发作期虚哮证的生物网络及镇喘保肺汤整体干预研究

Bronchial asthma is one of the world's most common chronic diseases. Traditional Chinese medicine (TCM) has some advantages for the treatment of chronic diseases, such as asthma. Recently, the development of network pharmacology and metabolomics provide useful tools for evaluating the TCM syndrome, herbal efficacy, and the netconnected mechanism of herbal intervention. This project is aimed to investigate the biological networks of the deficiency pattern of asthma in acute attack based on the TCM characteristics of holism and syndrome differentiation and treatment. The treatment of ZCBF Decoction, a clinical used formula, will also be studied. Systematic methods like metabolomics will be employed. The major contents include: (1) discovery of the biomarkers of the deficiency pattern of asthma in acute attack by comparing endogenous metabolites in blood or urine between normal and diseased samples; (2) evaluation of efficacy and network adjustment after treatment of ZCBF Decoction; (3) characterization of bioactive components and their metabolites in vivo of ZCBF Decoction for establishing relationship of syndrome-formulation-efficacy. This project will make it possible to connect the complex organism and herbal formulation, and to disclose the biomarkers of the deficiency pattern of asthma in acute attack.

支气管哮喘是全球最常见的慢性疾病之一，中医药在哮喘等慢性病上具有突出治疗优势，基于生物网络的代谢组学等研究方法为从整体上评估中医病证、中药药效及网络干预提供了强有力的手段。本项目以中医的整体观念和辨证论治思维为指导，以急性发作期虚哮证为研究对象，以临床有效方剂镇喘保肺汤为研究载体，运用基于生物网络的代谢组学等多学科方法，对正常、病理、给药后生物体的内源性代谢物组进行动态跟踪检测，借助多元数理统计手段，(1)系统揭示急性发作期虚哮证的生物标志物群，(2)研究镇喘保肺汤治疗急性发作期虚哮证的整体网络干预作用，(3)阐明镇喘保肺汤的药效物质基础及体内变化规律，构建病证-方剂-药效的有机关联。本课题搭建生物体和中药复方两个有机整体之间的桥梁，为中药复方的化学物质基础研究以及成分-药效-证候-生物网络调节的相关性提供示范。

目的:从基于生物网络的代谢组学层面对急性发作期虚哮证模型开展研究，明确支气管哮喘中医急性发作期虚哮证在大鼠及人体生物标志物群；验证镇喘保肺汤治疗急性发作期虚哮病证的整体网络干预作用；阐明镇喘保肺汤的主要药效物质基础，构建病证-方剂-药效的有机关联。.方法:①采用多因素复合病因建立模型。②采用NMR 、HPLC-MS、HPLC-(Q) MS分析血样、尿样。③采用PCR 和PLS-DA模式识别分析,确定代谢差异物。④对人参进行液相色谱检测，细分人参中有效成分。.结果:①成功建立急性发作期虚哮证大鼠模型；验方多角度多指标改善急性发作期虚哮证大鼠情况（P<0.01）。②正常组与急性哮喘组的主成分分析表明，两组之间具有代谢差异；PLS-DA分析得到差异性高表达代谢物。③PLS-DA分析显示R2Y和Q2 均大于0.4，模型可靠。④差异代谢物主要有磷脂类，脂肪酸类，还包括氨基酸类及糖类代谢物。.结论:①急性发作期虚哮证血清中 T、Cor 、T4 等含量明显降低。②急性发作期虚哮证大鼠模型和临床人体的确存在差异代谢物，且表明部分差异代谢物受验方影响大，验方组疗效佳。③验方可能对不同的磷脂类，脂肪酸类进行上/下调来达到治疗作用。④重点分析药物中人参成分在人体中变化规律，明确说明对肾气虚有改善作用。.