冠心病中医证型的比较脂质组学研究

Coronary heart disease（CHD） is clinical common disease and frequently-occurring disease,which belonging to the "chest discomfort" category.coronary atherosclerosis（AS） is the basic pathological the characteristics of coronary heart disease, Lipid metabolism disorder is an important risk factor of coronary atherosclerosis. Coronary heart disease patients often with dyslipidemia.There are different TCM syndrome type of coronary heart disease based on common pathophysiological Characteristics. At present, CHD have a variety of TCM syndromes and lack of objective standard. Lipidomics is a new method of lipid metabolism disorder syndromes which could differentiate TCM syndrome type . The national standard - " Chinese medicine ( Medicine ) clinical research guiding principle " )would be selected as classification basis for TCM syndrome type of coronary heart disease.This study is about comparison lipidomics of TCM Syndromes of coronary heart disease based on mass spectrometric detection platform to by analyzing blood and urine samples of the clinical patients with combined with multivariate statistical analysis, data mining technology to establish the evaluation criteria of TCM Syndrome by using lipidomics , discoverying and identifying special lipid biomarkers, clarifying lipid metabolism substance spectrum change trend, regularities and similarities and differences of the different TCM Syndrome types to providing syndromes objective basis of coronary heart disease .

冠心病为临床常见病、多发病，属于中医"胸痹"范畴。冠状动脉粥样硬化是冠心病的基础病理学特征，脂质代谢紊乱是冠状动脉粥样硬化的重要危险因素，冠心病患者多伴有血脂异常。具有共同病理生理学基础的冠心病在中医证型上表现各异。目前冠心病的证侯分型多样化，缺乏客观标准，脂质组学是脂代谢紊乱疾病证侯分型的新方法。 鉴于目前缺乏公认的证侯动物模型，课题组拟通过临床基础试验进行冠心病患者的比较脂质组学研究。以国家标准-《中药（新药）临床研究指导原则）》为冠心病中医证候的分型依据，采集冠心病患者血样、尿样并提取脂质组进行液质联用检测，结合多元统计、数据挖掘技术，建立以脂质组学为"评测尺度"的冠心病中医证侯分型方法，发现并鉴定特征性脂质生物标记物，阐明不同证型脂质代谢轮廓变化规律、趋势、异同及与证型的相关性，探讨冠心病不同证型的物质基础，以期从脂质组学角度为冠心病证候客观化提供依据。

冠心病是临床常见病，具有共同病理生理学基础的冠心病中医证型表现各异，证侯分型缺乏客观标准，证型客观化对于冠心病诊治具有积极意义。脂质代谢紊乱是冠心病的重要、独立危险因素，基于脂质组学的冠心病证型研究有利于提高临床辨证的客观性和精准性。. 课题组以《中药（新药）临床研究指导原则》为冠心病中医证型分型依据，在充分领会、消化辨证标准的基础上，为冠心病患者逐一准确辨证分型，累计采集健康志愿者和八种证型冠心病患者共170余例血样、尿样。以超高效液相-飞行时间质谱联用仪（UPLC-Q/TOF MS）为主要检测仪器，通过优化血浆与尿液脂质组提取方法及分析参数，建立了灵敏、稳定、可靠、高效的血浆、尿液脂质组学分析方法。正、负离子模式下进行了人血浆脂质组学研究，并在国内较早进行了人尿液脂质组学研究，累计获得约630G脂质组学原始数据。. 综合采用主成分分析（PCA）、正交偏最小二乘判别分析（OPLS-DA）等无监督和有监督的多元统计方法对人血浆和尿液脂质组学数据进行模式识别，结果表明健康志愿者和冠心病患者群体血浆、尿液脂质组学特征存在显著差异。通过对冠心病八个中医证型的脂质组学数据分析，所建立的以脂质组学为“评测尺度”的冠心病中医证型评价方法能有效区分大多数冠心病中医证型。对比健康人群与冠心病患者脂质组学数据，获得并确认区分健康人群和冠心病患者的脂质标志物，进而对冠心病患者八个证型亚群体间进行比较脂质组学分析，识别各个证型的脂质代谢特征，结合病理生理学作用、代谢通路及其生物学意义等确认各个证型的特征性脂质标志物。本课题研究将有助于阐明冠心病不同证型脂质代谢轮廓、异同，明确冠心病不同证型的物质基础，从脂质组学角度为冠心病证型客观化提供依据。