基于卵泡液代谢组学的肾阳虚型自然流产中医证候学研究

TCM Syndromes of Kidney-Yang Deficiency Spontaneous Abortion Based on Follicular Fluid Metabonomics

目的:探讨与肾阳虚型自然流产发生相关的卵泡液(follicular fluid,FF)代谢物组,以期为科学预测和诊断自然流产肾阳虚证、探讨其证候本质做初步尝试。方法:利用超高效液相色谱-高分辨质谱(HPLC-MS)技术对因输卵管因素行体外受精-胚胎移植(IVF-ET)的肾阳虚型自然流产患者即肾阳虚流产组(n=32)及分娩者即对照组(n=40)的卵泡液进行代谢组学分析。结果:肾阳虚流产组及对照组卵泡液共计32种差异代谢物,主要有氨基酸类、胆固醇类、维生素类、脂肪酸类、胆酸类、溶血卵磷脂类以及其它等七大类,其中上调的有Dehydroepiandrosterone sulfate,LysoPC(16:0),Palmitoylglycerophosphocholine等8种,下调的有L-valine,6-Oxohexanoate,L-Phenylalanine,2-Oxoglutarate,Linoleate等24种。结论:本研究鉴定的32种特征性化合物与中医肾阳虚证存在相关性,为肾阳虚型自然流产提供可能的诊断依据和治疗靶点,从FF代谢组学层面丰富发展了中医证候学。

Objective:To explore the metabolite group of follicular fluid(FF)associated with spontaneous abortion with deficiency of kidney-Yang in order to make a preliminary attempt for the scientific prediction and diagnosis of spontaneous abortion with deficiency of kidney-Yang and exploring the nature of its syndromes.Methods:Follicular fluid metabonomics analysis was performed on kidney-Yang abortion group(n=32)and control group(n=40)who underwent in vitro fertilization-embryo transfer(IVF-ET)by ultra-high performance liquid chromatography-high resolution mass spectrometry.Results:There were 32 kinds of different follicular fluid metabolites between kidney-Yang abortion group and control group,including amino acids,cholesterol,vitamins,fatty acids,bile acids,lysolecithin and others.Up-regulated ones were Dehydroepiandrosterone-sulfate,LysoPC(16:0),Palmitoy-lglycerophosphocholine and other 5 metabolites and down-regulated 24 species included L-valine,6-Oxohexanoate,L-Phenylalanine,2-Oxoglutarate,Linoleate and so on.Conclusions:Thirty-two differential metabolites identified in this study are related to kidney-Yang spontaneous abortion and provide a possible diagnostic basis and therapeutic target for kidney-Yang spontaneous abortion.From the perspective of FF metabolomics,TCM syndrome has been developed abundantly.