基于代谢组学和舌脉诊客观指标的变化特征研究益气复元膏方改善气虚质的机制

The constitution of Qi Deficiency is the most common biased constitution, and the herbal paste for regulating and nourishing body in winter is an important method for the intervention of qi deficiency, which belongs to the pre-treatment of disease. Our previous study confirmed that Yiqi Fuyuan paste can improve the symptoms of qi deficiency and the objective index of TCM diagnosis, changing the constitution from qi deficiency to gentleness, but its mechanism is not clear. Based on research reports of the relationship between metabonomics and TCM constitution,metabonomics is approved to be objectivity and feasibility in testing different syndromes and prescriptions of TCM. We hypothesize that there will be an objective difference in the metabonomics pattern between qi deficiency and gentleness, and it will show a dynamic variation with the time of intervention. We speculate that the metabonomics pattern of qi deficiency will tend to the pattern of gentleness after intervention of Yiqi Fuyuan paste. According to the former research, this project is going to systematic study the characteristics and changing path of metabonomics pattern and objective index of TCM diagnosis between study groups through one year observation by combing the detection technique of metabonomics and objective index of TCM diagnosis. The goal of this project is to explain the correlation between metabonomics and the objective index of TCM diagnosis on Qi deficiency, so as to investigate the mechanism of Yiqi Fuyuan paste on Qi deficiency constitution.

气虚质是最常见的偏颇体质，“冬令膏方调补”是干预气虚质的重要方法，属于中医治未病的范畴。本课题组前期研究证实益气复元膏方可以改善气虚质的症状及中医舌脉诊客观化指标，促使气虚体质向平和质转变，但其发挥作用的机制尚不明确。基于中医体质相关的代谢组学研究报道，显示代谢组学在辨证论治和以方测证方面存在客观性、可行性，我们推测气虚质与平和质代谢组学图谱存在生物标志物的差异，且随着时间进展和中医干预作用各自呈现规律的动态演变；而通过益气复元膏方的干预，气虚质代谢组学图谱的变化轨迹将趋向于平和质。本课题拟在前期研究基础上，结合代谢组学和中医舌脉诊等客观指标检测技术，通过一年的临床观察，系统研究气虚质与平和质的代谢图谱和中医客观指标的演变规律，以及益气复元膏方对气虚质干预的代谢图谱和中医客观指标的的变化特征。藉此阐释气虚质代谢组学与中医客观化指标的相关性，探讨益气复元膏方对气虚体质的作用机制。

本研究观察益气复元膏方干预前后气虚体质人群的中医体质状态改善状况，并同时分析中医舌诊、脉诊的客观数据，观察其变化特点。血清与尿液蛋白质组学用于中医体质客观化生物指标以及膏方干预的作用机制等研究。寻找平和体质与气虚体质血清和尿液中差异表达的炎症因子。同时寻找气虚体质治疗后（干预）差异表达的炎症因子。进一步探索平和体质与气虚体质的发病机制和信号通路，同时探索两种体质及干预前后的作用机制对信号通路和蛋白质组学的影响。治疗组患者服用膏方后气虚体质的症状改善状况，前后差异具有统计学意义（P＜0.05）。治疗组膏方干预后患者脉图信息指标中H3/H1降低、W2增高，通过HSV模型和Lab模型分析舌象图像，治疗组膏方干预后Lab-L、Lab-A值降低，差异有统计学意义（P<0.05）。气虚质对照组与平和质组对比在血清中存在有14种差异蛋白表达，在尿液中存在有18种差异蛋白表达。气虚质治疗组与气虚质对照组相比在血清中有共有12种差异蛋白表达。相对于气虚质对照组与平和质差异蛋白的上调，通过益气复元膏方的干预后，有相同的11种差异蛋白下调。 结果：益气复元膏方可以改善气虚体质人群的气虚症状表现。益气复元膏方纠正气虚体质的作用在舌脉诊客观指标上有所体现。气虚质与平和质在血清与尿液蛋白表达图谱中存在生物标志物的差异。气虚质治疗组与气虚质空白对照组在经膏方干预后血清中存在下调的差异蛋白，可能与相关信号通道的抑制有关。