Application of succinic acid in diagnosis or treatment of spontaneous abortion

A technology for spontaneous abortion and succinic acid, which is applied to medical preparations, pharmaceutical formulations, and drug combinations containing active ingredients, can solve problems such as no reports of succinic acid diagnosis or treatment of spontaneous abortion, and can reduce the level of succinic acid, embryonic Increased absorption rate, proliferative and invasive effects

Active Publication Date: 2022-06-28
SHANGHAI FIRST MATERNITY & INFANT HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, there is no report on the use of succinic acid in the diagnosis or treatment of spontaneous abortion

Method used

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  • Application of succinic acid in diagnosis or treatment of spontaneous abortion
  • Application of succinic acid in diagnosis or treatment of spontaneous abortion
  • Application of succinic acid in diagnosis or treatment of spontaneous abortion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 Analysis of the level of succinic acid in the villi and decidua of normal pregnant women and spontaneous abortion patients

[0033] The villus and decidua tissues of 30 pairs of normal pregnant women and patients with recurrent spontaneous abortion (RSA) were collected, and metabolic profiling was performed using nuclear magnetic resonance (NMR), and more than 95% of the samples were detected including glucose, amino acids, fatty acids and choline metabolic pathways various types of metabolites. Among these metabolites, we found 27.5% lower succinate levels, 22.4% higher fumaric acid levels, and 21.1% lower lactate levels in the villi of RSA patients than controls (Table 1). However, the levels of each metabolite in decidual tissue were not statistically different (Table 2).

[0034] Table 1: Metabolite concentrations in the villi of normal pregnancy and spontaneous abortion patients

[0035]

[0036]

[0037] Note: Normal: villus tissue of normal preg...

Embodiment 2

[0041] Example 2 Succinic acid promotes trophoblast proliferation and invasion

[0042] When treated with dimethyl succinate (DMS), JEG3 and HTR8 cells were plated at 2 × 10 3 The density of cells / well was placed in a 96-well plate (37°C, 5% CO 2 ), treated with 2 mM DMS for 24-96 hours. The medium was changed every day until the cells were harvested, then incubated with CCK-8 solution (C0039, Beyotime Biotechnology) for 2 h, and the absorbance was measured at 450 nm. The results show that DMS promotes trophoblast proliferation ( figure 1 ).

[0043] Invasion of JEG3 and HTR8 cells through Matrigel was objectively assessed by counting the number of cells in the invasion chamber that had migrated through the cell membrane. 15 μL of Matrigel (BD Biosciences) was pre-coated on a PET membrane (8 μm pore size, 6.5 mm diameter) on the upper surface of the filter of a Transewell plate (24-well plate, Corning, New York, USA) and air-dried under sterile conditions. Matrigel was tr...

Embodiment 3

[0044] Example 3 Establishment of low succinate mouse model

[0045] Cellular experiments confirmed that glycine reduces succinate levels in trophoblast cell lines HTR8 and JEG3 ( image 3 ), intraperitoneal injection of glycine can reduce the level of succinate in mouse villus tissue ( Figure 4 ). In order to explore the effect of low succinic acid level on embryo implantation and spontaneous abortion, we selected 8-week-old female C57BL / 6 mice (weight 20-30 g, n=24) and randomly divided them into three groups: control group (intraperitoneal injection of normal saline), Glycine intraperitoneal injection group (glycine: 1500 mg / kg / day) and glycine+DMS intraperitoneal injection group (glycine: 1500 mg / kg / day+DMS: 3000 mg / kg / day). See vaginal suppository as 0.5 days of pregnancy, intraperitoneal injection from 0.5 days to 5.5 days, and the embryo absorption rate and the number of implanted embryos were counted on the 14.5th day. We found that intraperitoneal injection of gly...

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Abstract

The present invention relates to the application of succinic acid in diagnosis or treatment of spontaneous abortion. The present invention compared the concentrations of glycolytic and citric acid cycle metabolites in the villi and decidua of normal pregnancy and those with recurrent abortion (RSA) by metabolic mass spectrometry, and found that succinic acid was low in the villi of embryos from patients with RSA. level; in vitro succinic acid treatment can promote the proliferation and invasion of trophoblast cells HTR8 and JEG3; at the same time, in vivo experiments confirmed that succinic acid intraperitoneal injection can reduce glycine-induced spontaneous abortion mouse model and CBA / J×DBA / 2 spontaneous abortion model embryo Absorption rate, thus providing a new method for the diagnosis and treatment of RSA clinically. The present invention also reduces the level of succinic acid in mice by intraperitoneally injecting glycine, leading to an increase in the absorption rate of mouse embryos, and establishes a new spontaneous abortion mouse model that is consistent with clinical phenomena and has a clear mechanism.

Description

technical field [0001] The present invention relates to the field of disease diagnosis and treatment, in particular to the application of succinic acid in diagnosis or treatment of spontaneous abortion. Background technique [0002] Three or more consecutive spontaneous abortions before 20 weeks of gestation are called recurrent spontaneous abortions (RSA) and affect 1% to 2% of women of reproductive age worldwide. Although etiological studies have reported various factors affecting RSA, excluding genetic factors, anatomical factors, endocrine factors, infectious factors, immune dysfunction, prethrombotic state, systemic diseases in pregnant women, and environmental factors, there are still most cases of RSA. Not explained. The researchers believe that the dysregulation of the microenvironment at the maternal-fetal interface may be the root cause of such unexplained recurrent miscarriages, but the relevant mechanism is still unclear, so there is no effective targeted interv...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/194A61P15/06G01N33/50
CPCA61K31/194A61P15/06G01N33/50
Inventor 金莉萍赵健元王晓辉许沙
Owner SHANGHAI FIRST MATERNITY & INFANT HOSPITAL
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