Study On The Distribution Of TCM Syndromes And Correlation With Follicular Fluid Metabonomics In Spontaneous Abortion Patients

Objective:To investigate the distribution of TCM syndromes and clinical symptoms in patients with spontaneous abortion by using clinical epidemiological investigation and research methods.Using follicular fluid(FF)metabonomics technology to analyze the FF components of kidney-Yang deficiency unexplained recurrent spontaneous abortion(URSA)and normal childbirth by In vitro fertilization and embryo transplantation(IVF-ET)and explore the mechanism of URSA,this study was to identify and determine the compound which has a close relationship with kidney-Yang deficiency URSA to investigate the correlation between FF metabolic markers in patients with URSA and kidney-Yang deficiency,In order to do a preliminary attempt to predict and diagnose kidney-Yang deficiency URSA and explore the nature of the syndromeMethods:By the method of clinical epidemiological investigation,a total of 264 cases of spontaneous abortion patients from the Department of Reproductive and Genetics of Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2016 to July 2017 were enrolled in this study.Data of four TCM clinics were collected to establish a database to analyze patients with spontaneous abortion TCM syndromes and distribution of clinical symptoms.On the basis of the first part of the study,using retrospective observational methods,the FF of IVF-ET patients(IVF due to tubal factors)in our center from May 2016 to February 2017 were collected and divided into control group(childbirth)40 cases and URSA group(kidney-Yang deficiency)32 cases,the FF of the two groups were analyzed by ultra performance liquid chromatography-high resolution mass spectrometry,and the data were processed by principal component analysis and partial least squares-discriminant analysis.Analyze FF difference metabolites in control group and kidney-Yang deficiency URSA group,to explore the correlation between FF metabolic markers in patients with URSA and kidney-Yang deficiency.Results:The epidemiological survey results:1.Among 264 patients with spontaneous abortion,kidney deficiency,a total of 196 cases(74.24%),is the most important TCM syndrome types of patients with spontaneous abortion,kidney-Yang deficiency is the most common type of kidney deficiency.Common TCM syndrome type of kidney-Yang deficiency are 47 patients(17.80%),kidney deficiency syndrome and kidney Yin and Yang deficiency syndrome,are 40 cases(15.15%),liver kidney deficiency 28 cases(10.61%),kidney deficiency heat syndromes of 17 cases(6.44%),kidney-Yin deficiency syndrome 14 cases(5.30%),liver depression syndrome in 11 cases(4.17%),blood heat syndrome 7 cases(2.65%),6 cases of kidney blood stasis syndrome(2.27%),5 cases of blood stasis syndrome(1.89%),liver kidney blood heat and blood deficiency syndrome all 3 cases(1.14%),spleen and kidney Yang deficiency syndrome,qi and Yin deficiency syndrome each 1 case(0.38%).2.The most common symptom in 264 cases of spontaneous abortion is waist and knee pain,fatigue and irritability are also more common.The experiment results:1.There are 32 kinds of different compounds between spontaneous abortion group and control group,including amino acids:L-valine,6-Oxohexanoate,2-Oxoglutarate,L-Leucine,L-Phenylalanine,Tryptophan;fatty acids:Linoleate,Oleic acid,Docosahexaenoic acid,Palmitic amide;Bile acids:Lithocholic acid,Chenodeoxyglycocholate,Trihydroxy-5beta-cholestan-26-al;vitamins:25-HydroxyvitaminD3,13'-hydroxy-alpha-tocopherol;lysolecithin:LysoPC(16:0),LysoPC(18:0),LysoPC(18:1),LysoPC(18:2),LysoPC(18:3),LysoPC(20:3),Ly soPC(20:4),LysoPC(20:5);Others:Palmitoylglycerophosphocholine,bilirubin,Hexadecanal,13,14-Dihy droretinol,Dehydroepiandrosterone-sulfate,Hydroxy cholesterol,Stearoylcarnitin e.2.The differential expression of Dehydroepiandrosterone sulfate,LysoPC(16:0),LysoPC(18:1),LysoPC(18:2),LysoPC(18:3),LysoPC(20:3),LysoPC(20:4)and Palmitoylgl-ycerophosphocholine in FF of kidney-Yang deficiency URSA patients was significantly higher than that in normal FF patients.L-valine,6-Oxohexanoate,L-Phenylalanine,25-HydroxyvitaminD3,Hydroxycholesterol,Chenodeoxyglycocholate,Trihydroxy-5beta-ch olestan-26-al,13'-hydroxy-alpha-tocopherol,LysoPC(18:0),LysoPC(20:5),Bilirubin and other expressions were down.Conclusion:1.Clinical epidemiological survey shows that the TCM syndromes of patients with spontaneous abortion are kidney deficiency syndrome and kidney-Yang deficiency syndrome is the main classification of kidney deficiency syndrome,which is in line with the theory of "kidney reproductive" in traditional Chinese medicine2.The most common symptom in 264 cases of spontaneous abortion is waist and knee pain,increased frequency of the appearance of symptoms such as irritability,may be related to changes in current social lifestyles3.FF metabolomics analysis showed that the expression of amino acids,fatty acids,vitamins and cholesterol are correlated with kidney-Yang deficiency.The expression of lysophosphatidylcholine,amides and DHEA in FF of URSA patients with kidney-Yang deficiency were significantly up-regulated,which may be related to the kidney-Yang deficiency syndrome,but still need further study4.The identified compounds identified as potential diagnostic criteria and therapeutic targets for URSA of kidney-Yang deficiency,and provide a scientific basis for the syndrome of kidney-Yang deficiency URSA from FF metabolomics level.