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Application of fructose 1,6-diphosphate (FDP) in preparation of fetus protection medicine for spontaneous abortion

A fructose diphosphate, spontaneous abortion technology, applied in the field of biomedicine, can solve the problem of unclear molecular mechanism of RSA

Active Publication Date: 2018-08-10
THE OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the molecular mechanism of these abnormal biological events at the maternal-fetal interface leading to RSA is still unclear. Therefore, the research on pregnancy-related diseases caused by abnormal maternal-fetal interaction dialogue is facing major challenges and opportunities. Based on these mechanisms, RSA Early warning and intervention strategies to be established

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  • Application of fructose 1,6-diphosphate (FDP) in preparation of fetus protection medicine for spontaneous abortion
  • Application of fructose 1,6-diphosphate (FDP) in preparation of fetus protection medicine for spontaneous abortion
  • Application of fructose 1,6-diphosphate (FDP) in preparation of fetus protection medicine for spontaneous abortion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Embodiment 1 analyzes the concentration of 1,6-fructose diphosphate in the peripheral blood, endometrium or decidua of non-pregnant, early pregnant and RSA patients

[0055] 1) The concentration of fructose 1,6-bisphosphate in peripheral blood and decidua decreased in RSA patients

[0056] First, using the 1,6-diphosphate fructose detection kit (Qingdao Jieshikang Co., Ltd.), it was found that compared with non-pregnant women, the concentration of peripheral blood 1,6-diphosphate fructose increased in early pregnancy women, and was higher than that of RSA patients ( Such as figure 1 Shown in A); Compared with the endometrial tissue of non-pregnant women, the concentration of 1,6-diphosphate fructose in the decidua tissue of early pregnant women increased, and was higher than that of RSA patients (such as figure 1 shown in B).

[0057] 2) The concentration of fructose-1,6-bisphosphate in the uterus of spontaneous abortion model mice decreased

[0058] After constructi...

Embodiment 2

[0059] Example 2 The in vivo experiment confirmed that the supplementation of fructose 1,6-diphosphate significantly improved the pattern of uterine immune tolerance in spontaneously aborted pregnant mice

[0060] Using flow cytometry (all flow cytometry antibodies come from BioLegend), it was found that, compared with control pregnant mice, the CD45 + F4 / 80 + Decreased expression of M2 phenotype molecules (CD206, CD209 and IRF4) in macrophages, CD45 + CD4 + GATA-3 + Helper T(Th)2 and CD45 + CD4 + Foxp3 + The proportion of regulatory T cells decreased; in contrast CD45 + CD4 + T-bet + Elevated Th1 cells (eg image 3 shown). The spontaneous abortion pregnant mice group was intraperitoneally injected with 1,6-diphosphate fructose (the method is the same as above) or control saline, and the uteri of pregnant mice were collected on the 14th day of pregnancy. The ratio of M2 macrophages, Th2 and Treg cells in the uterus of spontaneous abortion pregnant mice was high, and...

Embodiment 3

[0061] Example 3 The in vivo experiment confirmed that the supplementation of fructose 1,6-diphosphate significantly improved the degree of uterine decidualization in spontaneously aborted pregnant mice

[0062] Real-time RCR (Takara was purchased from Takara Company) was used to analyze and find that, compared with control pregnant mice, the decidualization-related genes Lif, Prlr, IL11, Ihh, Igfbp1, dPRP, Cebpb, Hoxa10, The transcript levels of Wnt4 and Bmp2 (primers were synthesized by Shanghai Sangon) were significantly reduced (eg Figure 4 shown). The spontaneous abortion pregnant mice group was intraperitoneally injected with 1,6-diphosphate fructose (the same method as above) or control saline, and the uteri of pregnant mice were collected on the 14th day of pregnancy. The transcription of the above decidualization-related genes in the uterus of spontaneously aborted pregnant mice (such as Figure 4 shown). It suggested that the supplementation of fructose 1,6-dipho...

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Abstract

The invention belongs to the technical field of medicines, and in particular discloses application of fructose 1,6-diphosphate (FDP) in preparation of a fetus protection medicine for spontaneous abortion. In vitro and in vivo animal experiments show that the concentration of the FDP in peripheral blood and decidual tissues of patients with recurrent spontaneous abortion is decreased compared withnormal pregnancy. Compared with control pregnant mice, the model plasma and uterus FDP levels of pregnant mice with spontaneous abortion are reduced, the uterus macrophage M2 phenotype molecule expression of the pregnant mice with spontaneous abortion is decreased, the proportions of helper cells T(Th)2 and regulatory T cells are reduced, and the phenomena of poor endometrium decidualization and decreased embryonic trophoblast infiltration degree occur in an accompanied way. The results indicate that the supplement of the FDP can significantly improve the uterine immune tolerance pattern, decidualization and embryonic trophoblast infiltration in the pregnant mice with spontaneous abortion, and obviously reduces embryonic loss in the pregnant mice. Therefore, the FDP is expected to be an early-warning and diagnostic indicator for the patients with spontaneous abortion, and can be used for preparing the fetus protection medicine for the spontaneous abortion.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of fructose 1,6-diphosphate in the preparation of medicine for spontaneous abortion. In vitro experiments and in vivo animal experiments showed that compared with normal pregnancy, the concentration of fructose 1,6-diphosphate in peripheral blood and decidua tissue of patients with recurrent spontaneous abortion decreased. Compared with control pregnant mice, the plasma and uterine FDP levels of spontaneous abortion pregnant mice decreased, the expression of M2 phenotype molecules in uterine macrophages decreased, the proportion of helper cells T (Th) 2 and regulatory T cells decreased, and endometrial Poor decidualization and reduced infiltration of embryonic trophoblasts. The above results indicated that 1,6-diphosphate fructose supplementation could significantly improve the pattern of uterine immune tolerance, decidualization and embryonic trophoblast infil...

Claims

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Application Information

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IPC IPC(8): G01N33/53G01N15/14A61K31/7024A61P15/06
CPCA61K31/7024A61P15/06G01N15/14G01N33/53
Inventor 李明清周文洁金莉萍
Owner THE OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIV
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