慢性胃炎湿证舌苔代谢物与胃镜特征相关性及诊断模型研究

Dampness syndrome is one of the common Traditional Chinese Medicine(TCM) syndromes of chronic gastritis(CG). In our previous researches we had found some differential protein molecules in tongue coating of patients with dampness syndrome of CG, some differential metabolic molecules in greasy tongue coating of patients with CG and the association between tongue information parameters, tongue coating immune index of patients and gastroscopy characteristics. Based on this foundation, we will use metabolomics methods based on the application of gas chromatography-mass spectrometry technology and liquid chromatography-mass spectrometry technology to detect metabolites in tongue coating of patients with dampness syndrome and non-dampness syndrome of CG, dampness syndrome of sub-health and normal: ①make a quantitative and qualitative analysis of tongue coating metabolites by means of multivariate data processing and bioinformatics methods, screening tongue coating metabolic markers CG dampness, identify the chemical structure and function of metabolic markers, and explain the metabolic pathway of dampness syndrome of CG; ②use the canonical correlation analysis to investigate the correlation between tongue coating metabolism markers and gastroscopic features of dampness syndrome of CG, through the support vector machine, decision tree, random forest and other methods to establish diagnostic model of dampness syndrome of CG based on tongue coating metabolite and endoscopic characteristics, and finally verify, evaluate and improve the model. This research will provide the experimental basis for the material basis and mechanism of dampness syndrome, and also provide the basis for the diagnosis, evaluation of therapeutic effect and prognosis of CG through exploring the use of noninvasive tongue coating metabonomics in the detection of assisted gastroscopy.

湿证是慢性胃炎（CG）常见证候之一。本课题组前期研究检测了CG湿证舌苔中差异蛋白和CG腻苔中差异代谢物，并发现CG舌象信息客观参数、舌苔免疫指标与胃镜特征之间存在相关性。基于此，本项目应用气-质联用、液-质联用等代谢组学技术检测CG湿证、CG非湿证、亚健康湿证和正常人舌苔中代谢物：①通过多元变量统计等数据处理及生物信息学方法对舌苔代谢物进行定量、定性分析，筛选CG湿证的舌苔代谢标志物，鉴定代谢标志物的化学结构及功能，阐释CG湿证的代谢通路等发生机制；②运用典型相关分析探讨CG湿证舌苔代谢标志物与胃镜特征的相关性，并基于舌苔代谢标志物及胃镜特征，通过支持向量机、决策树、随机森林等方法建立CG湿证诊断模型，最后对模型进行临床验证、评价及完善。以期为湿证的物质基础及发生机制提供代谢组学方面的实验依据；并通过探索用无创的舌苔代谢组学检测辅助胃镜检查，为CG病证诊断、疗效评价及预后监控提供研究基础。

湿证是慢性胃炎（CG）常见证候之一。CG患者舌苔变化与胃镜特征的相关性具有一定规律。本项目运用GC-TOF-MS和UHPLC-QE-MS代谢组学检测技术，通过生物信息学方法筛选CG湿证舌苔代谢物，并分析其与胃镜特征的相关性，得到如下结果：（1）CG湿证组与CG非湿证组比较有115种已知代谢物有显著性差异，分别属于脂质和脂质样分子、有机杂环化合物、有机氧化合物、苯环型化合物、有机酸及其衍生物、有机氮化合物、核苷/核苷酸和类似物、有机硫化合物、苯丙素和聚酮类化合物。CG寒湿证组与CG湿热证组比较有16种已知代谢物有显著性差异，分别属于脂质和脂质样分子、有机氧化合物、苯环型化合物、有机酸及其衍生物、有机氮化合物、有机硫化合物、苯丙素和聚酮类化合物。其中，脂质和脂质样分子是CG湿证与CG非湿证、CG寒湿证与CG湿热证的最主要差异代谢物。（2）CG湿证组与CG非湿证组比较共有49种差异代谢物涉及25条代谢通路，CG寒湿证组与CG湿热证组比较共有5种差异代谢物涉及5条代谢通路。其中，脂类物质代谢异常是CG湿证、CG寒湿证、CG湿热证的主要发生机制之一。（3）分析CG湿证舌苔代谢标志物与胃镜特征的相关性，发现与CG非湿证相比，6-脱氧甘露醇在CG湿证中显著下调，与胆汁反流呈负相关；四羧酸在CG湿证中显著上调，与萎缩呈负相关；1-磷酸蝶呤在CG湿证中显著下调，与肠化呈正相关。（4）通过筛选CG湿证与CG非湿证比较所得的舌苔差异代谢物构建的诊断模型，得到最佳模型由苯酚、2,6-二氨基丙酸和正十六烷基吡咯烷组成，随机检测50例CG患者的舌苔代谢物进行验证，显示该模型的准确度为93.9%。通过筛选CG寒湿证与CG湿热证比较所得的舌苔差异代谢物构建的诊断模型，得到最佳模型由苯酚组成，随机检测18例CG患者的舌苔代谢物进行验证，显示该模型的准确度为80.0%。本研究为CG湿证的物质基础及发生机制提供代谢组学方面的实验依据；并通过探索用无创的舌苔代谢组学检测辅助胃镜检查，为CG病证诊断、疗效评价及预后监控提供研究基础。本项目组成员以第一/通讯作者发表国内核心期刊论文3篇、SCI论文2篇；参加国内学术会议9人次、国际学术会议2人次，应邀学术报告2次；赴国外访学1人；指导硕士生1名、本硕连读生2名。