Research Of Quality Control And Study On The Medical-induced Incomplete Abortion Rats Based On Serum Metabolomics Of Buxue Yimu Preparation

Objective:The HPLC chemical fingerprint of 10 batches of Buxue Yimu Preparation was established,and the major five compounds of Buxue Yimu Preparation was determined.To explore the protective effect of Buxue Yimu Preparation on rats with incomplete abortion based on metabolomics,and to provide the basis for ensuring its clinical efficacy.Methods:The methodology for the determination of the content of index components was established and confirmed.The contents of five index components in different batches of Buxue Yimu Preparation were determined.At the same time,the HPLC chemical fingerprint of Buxue Yimu Preparation was established.Mifepristone（8.3 mg/kg）combined with misoprostol（100.0μg/kg）was used to establish the model of medical abortion in rats.After administration Buxue Yimu Preparation（4.32 g/kg）for 7days,the serum levels of human chorionic gonadotrophin（HCG）,estradiol（E₂）,and progesterone（Pg）were determined.Furthermore,hematoxylin-eosin staining（HE）was used to evaluate the histopathological changes in uterine tissue.The expression levels of VEGF and NF-κB were detected by immunohistochemistry.In addition,the serum endogenous metabolites were analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF/MS）.Multivariate analysis,including partial least squares discriminant analysis（PLS-DA）and orthogonal partial least squares discriminant analysis（OPLS-DA）,was employed to analyze the metabolic profiles and metabolic pathways.Results:The HPLC fingerprint of 10 batches of Buxue Yimu Preparation was established and 36 common fingerprint peaks was identified,the similarity of 10 batches of Buxue Yimu Preparation was greater than 0.96.The linearity relationships of leonurine,calycosin-7-O-glucoside,rutin,ferulic acid and ligustilide were good（r≥0.9999）.The content of leonurine,calycosin-7-O-glucoside,rutin,ferulic acid and ligustilide in 10batches of Buxue Yimu Preparation were 128.5-168.9,153.6-270.5,107.9-301.1,191.4-280.9,1812.2-3325.6μg/g,respectively.Among all the detected components,ligustilide accounted for the highest content.The results of animal experiments showed that Buxue Yimu Preparation could regulate the coagulation function of rats with medical abortion,reduce the pathological damage,promote the endometrial recovery,reduce the expression of NF-κB in uterine tissue,and promote the expression of VEGF in uterine tissue.The metabolism profiles of drug abortion model group and pregnancy control group were obviously separated,and Buxue Yimu Preparation gradually returned to normal after administration.A total of 19 potential biomarkers were identified,which were mainly involved in metabolism of amino acids,lipid metabolism and metabolic pathways related to bile acid biosynthesis.Conclusions:Buxue Yimu Preparation play a potential protective role in the intervention of drug abortion by anti-inflammatory,promoting endometrial repair and regulating metabolic disorders.