正常高值血压中医证侯宏观量化诊断标准的建立及其代谢机制

The present study is under the guidance of the theory of syndrome differentiation and preventive treatment of disease, combined with the modern predictive, preventive and personalize medicine based on the syndrome characterization and syndrome essense in prehypertension. By extracting the informations group of four diagnostic modes, diagnostic mathematical model and the classification standard will be built for clarifying the type and revealing the macro characteristic law of TCM syndrome in prehypertension. The prehypertension, comparing to hypertension patients and healthy volunteers, are observed and their blood will be collected for metabolic components isolation and analysis.The data of biomarker from metabolic will be applied to construct the mathematical model of prehypertension, the TCM syndrome in prehypertension and the evolution of different syndrome. Incorporation with the data of measure table study，the "disease-syndrome-metabolic" system of the TCM syndrome in prehypertension will contain the macro characteristic and objective metabolic model.The correspongding relation from external and interal of syndrome is clearly demonstrated and the scientific connotation of syndrome is explained reasonably. The TCM syndrome in prehypertension is diagnosed by the objective and scientific methods, which is value for creating the forward diagnosis and treatment mode embodying characteristics of TCM in hypertension.

本项目以中医"辨证思想"和"治未病"理论为指导，衔接现代预防医学、预测医学和个性化治疗方法，立足于正常高值血压的证候表征和内涵实质，提炼正常高值血压核心四诊信息组合，阐明正常高值血压中医证候类型，建立正常高值血压中医证候的诊断数学模型与程度分级标准，从而揭示其中医证候的宏观表征规律。以此为据，以正常高值血压受试者为研究主体，并与高血压病患者和健康志愿者作横向比较，采集血液标本经代谢组学分析，提取代谢组学生物标记物数据，分别构建正常高值血压、正常高值血压不同中医证侯特征、正常高值血压中医证侯演变的数学模型，结合量表学、证侯的数据分别作为组成模块，建立涵盖中医证侯的宏观表征和客观代谢模式为一体的正常高值血压"病-证-组"系统，清晰展现证侯外延和内涵的对应关系，合理诠释中医证侯理论的科学内涵，实现正常高值血压中医证侯的可视化、科学化诊断，从而构建体现中医特色的高血压病前移的诊治模式。

以中医辨证思想和治未病理论为指导，采用流行病学调查方法，收集正常高值血压人群的四诊信息，并对其进行描述性统计分析, 得出正常高值血压人群有头痛、头晕、腰膝酸软等36种常见的症状及体征；进而采用探索性因子分析和聚类分析等无监督的方法，挖掘正常高值血压四诊信息数据，正常高值血压人群可分为无症状组、肝火炽盛证、痰湿壅盛证、肾阳虚证和阴虚阳亢证五大类；采用循证医学的方法建立的正常高值血压常见中医证候诊断量表和量化诊断标准，经过综合测评，证实该诊断标准信度、效度、反应度较好，正常高值血压阴虚阳亢证、痰湿壅盛证、肝火亢盛证的量化诊断标准具有良好的可行性、准确性和临床使用价值，该研究成果将为正常高值血压常见中医证候的进一步深入研究提供标准化尺度；进而以正常高值血压患者为研究主体，并与高血压病患者和健康志愿者作横向比较，进行代谢物组分的分离与分析，筛选出了正常高值血压人群阴虚阳亢证、痰湿壅盛证、肝火亢盛证的特征性代谢标志物，并确定其特征性代谢通路和代谢网络；立足于正常高值血压的证候表征和内涵实质，整合宏观表征数据和微观代谢数据，包括烦躁易怒、头胀、口干、口苦、尿赤等5个宏观证候表征，鞘氨醇1-磷酸盐、脱氢表雄酮硫酸盐、肾上腺素等12个代谢标志物，通过PLS回归模型筛选出对中医证候判别模型的构建贡献较大的宏、微观指标，揭示了正常高值血压中医证候外在宏观四诊与内在代谢标志物的对应关系，构建了正常高值血压的“病-证-组”同步表达系统。.该研究实现了宏微观数据的有机结合，通过代谢组学技术升华了“治未病”理论，从而对接了预防医学、预测医学、个性化医学和转化医学，保持中医原创性的同时融合现代科学技术，清晰展现了证侯外延和内涵的对应关系，合理诠释了中医证侯理论的科学内涵，实现正常高值血压中医证侯的可视化、科学化诊断，构建了体现中医特色的高血压病治疗前移的宏微观诊断模式，从而为中医临床高血压病前移的提供诊断基础。