Analysis Of Serum Metabonomics In The Treatment Of Ovarian Endometriosis Cyst With Leapromarelin Acetate

Objective: This study was based on the metabonomics platform of ultra-high performance liquid chromatography-mass spectrometry(HPLC-MS)to investigate the changes of plasma metabonomics in the treatment of ovarian endometriosis cyst with lepirelin acetate.Method:1.Cases Selection:Twenty-six patients who underwent laparoscopic conservative surgery and pathologically proved by pathology in Dalian Maternal and Child Health Care Hospital were collected from November 2017 to August 2018.The patients were divided into SG group(n = 16)and operation group(S group,n = 10)according to whether or not the patients were assisted in the use of leuprorelin acetate(Shanghai Lizhu Pharmaceutical Co,Ltd,H20093852).The patients with the combined treatment group received a subcutaneous injection of leuprolide acetate at 3.75 mg on the first to five days after the operation,and the drug was injected once every 28 days and the drug was continuously used for three months.2.Experiment method:The fasting venous blood 2 ml,centrifugal force 3 000 r,centrifugation 5 min were taken from the patients of the combined treatment group and the patients of the simple operation group at the end of treatment and three months after the operation,respectively.The supernatant was labeled and stored in the refrigerator at-80 ?.Before the experiment,the samples were taken out,thawed and pretreated,and the serum samples of two groups of patients were detected by ultra-high performance liquid chromatography-four-stage rod-electrostatic field orbital well high resolution mass spectrometry(UPLC-Q Exactive).The metabolic spectrum and the original data file were obtained.3.Data processing and pattern recognition:The original data was imported into the compound discovery 2.1 operating software produced by ThermoFisher Company for pretreatment,and the missing values were removed according to the 80% principle of the obtained data.Then the MetaboAnalyst4.0 software was imported for principal component analysis(PCA),).Partial least squares discriminant analysis(PLS-DA)was used to screen differential metabolites according to variable weight value(Variable important projection,VIP)combined with T-test results.The receiver operating characteristic curve(receiver operating characteristic curve,ROC)was established,and the area(AUC)values under the ROC curve were compared to find out the differential metabolites with great differentiation value,and the metabolic pathways of the differential metabolites were analyzed.Result:(1)in this study,we successfully constructed the PCA,PLS-DA model of the combination group and the simple operation group in the positive ion mode.In the PCA,PLS-DA model,the two groups could be separated obviously.(2)There were 24 serum metabolites with significant difference between the combination group and the single operation group.Compared with the simple operation group,In the combined group,Uracil?N1-Methyl-2-pyridone-5-carboxamide?Alanyl-Glutamic acid?Uridine?Citrulline?LPC(18:0)?LPC(20:1)?LPC(20:2)?LPC(20:3)?LPC(16:0e)LPE(20:4),?Isovaleryl carnitine?N(6)-Methyllysine?L-Kynurenine?Seryl-valine were raised,while Methionine sulfoxide?L-Isoleucine?L-Serine?Sphingosine 1-phosphate?Isoleucyl-proline?SM(d36:1)?SM(d36:2)?L-Phenylalanine decreased.(3)By ROC curve analysis,it was found that the seven metabolites had good differentiation value,L-Isoleucine ?L-Serine?Methionine sulfoxide?SM(d36:1)?SM(d36:2)?Ile-Pro[Isoleucyl-proline] ? Sphingosine 1-phosphate which were respectively.(4)the differential metabolic pathways were mainly involved in four metabolic pathways:aminoacyl-tRNA biosynthesis,pyrimidine metabolism,arginine and proline metabolism,and sphingolipid metabolism.Conclusion:The metabonomics technique based on HPLC-MS technique revealed the detailed information of plasma metabolic profiles of patients with chocolate capsule treated by combination of Laparoscopic and Laparoscopic surgery,and screened andidentified 24 differential metabolites.Seven differential substances with medium or higher differential value were screened.According to the metabolic pathway,the differential metabolites were mainly involved in four metabolic pathways:aminoacyl-tRNA biosynthesis,pyrimidine metabolism,arginine and proline metabolism,and sphingolipid metabolism.It may be related to the involvement of lepirelin acetate in antagonizing oxidative stress in endometriosis patients.These studies suggest that antioxidative stress drugs are expected to be new drugs for treatment of endometriosis.