基于代谢组学的多囊卵巢综合征痰湿证生物标志物筛选及燥湿化痰方药干预的研究

The preliminary study indicated that DHEA-S, FINS, HOMA-IR, SHBG, FAI, granular cell IRS-1mRNA, IRS-2mRNA and clinical characteristics, and pregnancy rate for patients in phlegm-dampness group of PCOS all have significant differences with non- phlegm-dampness group and control group.Based on this foundation, the project adopted the mode with tight combination of basic and clinical research ,took the serum and follicular metabolism as the breakthrough point, applied the metabonomics method that based on HNMR detection techniques to detect the endogenous small molecules metabolites of serum and follicular liquid in phlegm-dampness group, non- phlegm-dampness group and control group,by comparing the differences of metabolic map ,data processing and pattern recognition, this study made a qualitative and quantitative analysis for all small molecular compounds in serum and follicular liquid,looking for biological markers for Phlegm-dampness syndrome of PCOS, to establish the diagnosis model based on data for Phlegm-dampness syndrome of PCOS; And combined with the intervention of traditional Chinese medicine, comprehensively analysed the formation, transfer mechanism and process of endogenous metabolism products for phlegm-dampness syndrome of PCOS , discussed the pathogenesis for Phlegm-dampness syndrome of PCOS, gradually revealed its biological essence. To provide ideas and research basis in establishing related metabolic map, metabolic diagnosis model of disease and syndrome in traditional Chinese medicine.

课题组前期研究发现，多囊卵巢综合征（PCOS）痰湿证患者DHEA-S、FINS、HOMA-IR、SHBG、FAI、颗粒细胞IRS-1mRNA、IRS-2mRNA及临床特征、受孕率等与PCOS非痰湿组和对照组比较均有显著性差异。本项目在此基础上，立足基础与临床紧密结合的研究模式，以血清和卵泡液代谢组分为切入点，应用基于核磁共振氢谱(HNMR)检测技术的代谢组学方法，检测PCOS痰湿组、非痰湿组和对照组血清及卵泡液中的内源性小分子代谢物，通过比较各组代谢图谱的差异及数据处理、模式识别，对血清及卵泡液中所有小分子化合物进行定性、定量分析，寻找PCOS痰湿证的生物标志物，创建PCOS痰湿证基于数据的诊断模型；并结合中药干预，综合分析PCOS痰湿证内源性代谢产物的形成、转移机制和过程，探讨PCOS痰湿证的发病机理，逐步揭示其生物学本质。将为确立中医病证相关的代谢图谱、代谢诊断模型研究提供思路和依据。

课题组前期研究发现，多囊卵巢综合征（PCOS）痰湿证患者DHEA-S、FINS、HOMA-IR、SHBG、FAI、颗粒细胞IRS-1mRNA、IRS-2mRNA及临床特征、受孕率等与PCOS非痰湿组和对照组比较均有显著性差异。本项目在此基础上，立足基础与临床紧密结合的研究模式，以血清和卵泡液代谢组分为切入点，应用基于核磁共振氢谱(HNMR)检测技术的代谢组学方法，检测了PCOS痰湿组、非痰湿组和对照组血清及卵泡液中的内源性小分子代谢物，通过比较各组代谢图谱的差异及数据处理、模式识别，对血清及卵泡液中所有小分子化合物进行定性、定量分析。综合各组间的代谢组分差异发现了PCOS痰湿证患者血清中的乙醇、甘油磷酸胆碱、低密度脂蛋白L1明显降低，柠檬酸、乙酰乙酸、极低密度脂蛋白L5、脂质L7、乳酸、赖氨酸明显增加。这9种代谢物可能是PCOS痰湿证潜在的生物标志物。PCOS患者血清代谢组分的变化机制和三羧酸循环、糖代谢、脂类代谢和蛋白质代谢密切相关。主要表现为三羧酸循环障碍，糖代谢缓慢，脂肪和蛋白质代谢增强。PCOS痰湿证患者体内伴随着显著的三羧酸循环障碍和糖脂代谢异常，与PCOS非痰湿组相比，糖酵解增强及糖异生抑制更为明显，脂肪动员加强。提示PCOS痰湿证患者存在更为显著的糖代谢和脂肪代谢紊乱，胰岛素抵抗可能与此有潜在联系。而通过观察分析燥湿化痰中药对PCOS痰湿证组干预前后血清代谢组分的变化发现，干预后与干预前存在显著差异，尤其是痰湿证常见的特征性标志物的改变，说明燥湿化痰中药能显著改善PCOS痰湿证的内源性代谢产物，并改善其相应的糖脂代谢紊乱。本课题的相关研究结果为创建PCOS痰湿证基于数据的诊断模型提供了理论支撑，更深入的揭示了PCOS痰湿证的发病机理和生物学本质。为确立中医病证相关的代谢图谱、代谢诊断模型研究提供了思路和依据。