Application of succinic acid to diagnosis or treatment of spontaneous abortion

A technology for spontaneous abortion and succinic acid, which is applied to medical preparations containing active ingredients, material testing products, organic active ingredients, etc., and can solve problems such as no reports of succinic acid diagnosis or treatment of spontaneous abortion.

Active Publication Date: 2021-05-18
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 to diagnosis or treatment of spontaneous abortion
  • Application of succinic acid to diagnosis or treatment of spontaneous abortion
  • Application of succinic acid to diagnosis or treatment of spontaneous abortion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0033] The villi and decidua tissues of 30 pairs of normal pregnant women and patients with recurrent spontaneous abortion (RSA) were collected, and nuclear magnetic resonance (NMR) was used for metabolic profiling analysis. More than 95% of the samples were detected including glucose, amino acid, fatty acid and choline metabolic pathways various types of metabolites. Among these metabolites, we found 27.5% lower levels of succinate, 22.4% higher levels of fumarate, and 21.1% lower levels of lactate in the villi of RSA patients compared to controls (Table 1). However, there was no statistical difference in the levels of each metabolite in decidua tissue (Table 2).

[0034] Table 1: Concentrations of metabolites in villi of normal pregnancy and spontaneous abortion patients

[0035]

[0036]

[0037] Note: Normal: villous...

Embodiment 2

[0041] Example 2 Succinic acid promotes proliferation and invasion of trophoblasts

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

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

Embodiment 3

[0044] The establishment of embodiment 3 low succinic acid mouse model

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

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Abstract

The invention relates to an application of succinic acid to diagnosis or treatment of spontaneous abortion. The concentration of glycolysis and citric acid cycle metabolites in villus and decidua of people in normal pregnancy and with recurrent spontaneous abortion (RSA) is compared through metabolism mass spectrometry analysis, and it is found that the phenomenon of low succinic acid level exists in embryo villus tissue of an RSA patient; in-vitro succinic acid treatment can promote proliferation and invasion of trophoblasts HTR8 and JEG3; and besides, in-vivo experiments prove that succinic acid intraperitoneal injection can reduce the embryo absorption rate of a mouse model with glycine-induced spontaneous abortion and a CBA / J * DBA / 2 spontaneous abortion model, so that a new method is provided for clinical diagnosis and treatment of RSA. In addition, by intraperitoneal injection of glycine, the succinic acid level in the mouse body is reduced, the absorption rate of a mouse embryo is increased, and a new spontaneous abortion mouse model which conforms to a clinical phenomenon and is clear in mechanism is established.

Description

technical field [0001] The 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 abortions (RSA), affecting 1% to 2% of women of reproductive age worldwide. Although etiological studies have reported various factors affecting RSA, except genetic factors, anatomical factors, endocrine factors, infectious factors, immune dysfunction, prothrombotic state, systemic diseases of pregnant women, and environmental factors, there are still a large number of RSA cases. Not explained. Researchers believe that the microenvironmental imbalance at the maternal-fetal interface may be the root cause of such unexplained recurrent miscarriages, but the relevant mechanisms are still unclear, so there is no effective targeted intervention and treatment str...

Claims

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Application Information

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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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