Application of chemokine XCL1 in the preparation of drugs to prevent adverse pregnancy outcomes in advanced-age pregnant women

Abstract

The present invention discloses the use of chemokine XCL1 in the preparation of a drug for preventing adverse pregnancy outcomes in advanced-age pregnant women. The present invention discloses the use of chemokine XCL1 in preventing adverse pregnancy outcomes in advanced-age pregnant women, especially chemokine XCL1 improves fetal growth restriction, which plays an important role in the pregnancy process. By applying XCL1 recombinant protein, the phenotype of fetal growth restriction in advanced-age pregnant mice can be alleviated, the possibility of adverse pregnancy outcomes is reduced, and a new effective measure is provided for the clinical treatment of adverse pregnancy outcomes in advanced-age pregnant women in the late stage.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and more specifically, to the use of chemokine XCL1 in the preparation of a drug for preventing adverse pregnancy outcomes in advanced-age pregnant women. Background Art

[0002] Clinically, advanced maternal age (AMA) is defined as pregnant women aged 35 and above. Due to the influence of socioeconomic environment, higher education and assisted reproductive technology, the childbearing age of women around the world has changed significantly, and the population of AMA has been increasing year by year.

[0003] Adverse pregnancy outcomes refer to a series of adverse events and complications during childbirth that have serious effects on the health of the mother and fetus. For AMA, the risk of adverse pregnancy outcomes is higher, often accompanied by pregnancy complications, such as fetal growth restriction, premature birth and preeclampsia, and the prognosis of newborns in AMA is also poor.

[0004] Chemokines: a class of small cytokines or signaling proteins secreted by cells. They are named chemokines because they have the ability to induce directional chemotaxis of nearby reactive cells. Some chemokines are considered to be pro-inflammatory cytokines, which can induce immune cells to enter the infection site and produce inflammation during the immune response, while some chemokines are believed to regulate the body's life activities and play an important role in normal tissue maintenance or development.

[0005] During pregnancy, chemokines play a key role in the immune regulation of the maternal-fetal interface and the formation and development of the placenta. There are a large number of immune cells in the maternal-fetal interface of the placenta that maintain the stability of the maternal-fetal interface by secreting chemokines and their receptors. The rational division of labor in this complex network ensures the successful progress of pregnancy.

[0006] Chemokines cause uterine cells to preferentially recruit Th2 and Treg Th cells, which helps to form an immune-tolerant anti-inflammatory microenvironment. Adding chemokine CXCL12 to the abortion mouse model can prevent fetal loss. Placental CXCL3 reduces trophoblast invasion and angiogenesis, leading to preeclampsia. The occurrence of premature birth is associated with a decrease in CCL6. Abnormal expression of CXCL5 may lead to recurrent miscarriage. It can be seen that chemokines are essential for fetal growth and development, but there are currently no reports on the use of chemokines to treat adverse pregnancy outcomes in late AMA.

[0007] Other studies have reported that chemokine XCL1 (XC motif chemokine ligand 1, XCL1, Gene ID: 6375) promotes the migration and invasion of trophoblast cells by increasing the activity of matrix metalloproteinases at the maternal-fetal interface. However, there have been no reports on its correlation with adverse pregnancy outcomes in late AMA. Summary of the invention

[0008] The purpose of the present invention is to overcome the deficiencies of the prior art and provide an application of the chemokine XCL1 in the preparation of a drug for preventing adverse pregnancy outcomes in advanced-age pregnant women.

[0009] The first object of the present invention is to provide the use of chemokine XCL1 in preparing drugs for preventing adverse pregnancy outcomes.

[0010] The second object of the present invention is to provide the use of chemokine XCL1 in preparing a drug for alleviating fetal growth restriction.

[0011] In order to achieve the above object, the present invention is implemented by the following technical solutions:

[0012] Application of chemokine XCL1 in the preparation of drugs for preventing adverse pregnancy outcomes.

[0013] Preferably, the adverse pregnancy outcome is an adverse outcome in late pregnancy.

[0014] More preferably, the adverse pregnancy outcome is an adverse outcome in late pregnancy for older pregnant women.

[0015] Preferably, the adverse pregnancy outcome is an adverse pregnancy outcome of the fetus.

[0016] More preferably, the adverse fetal pregnancy outcome is fetal growth restriction.

[0017] Even more preferably, the fetal growth restriction is fetal weight loss.

[0018] Even more preferably, the fetal growth restriction is caused by decreased placental weight.

[0019] Even more preferably, the fetal growth restriction is a shortening of the fetal body length and / or tail length.

[0020] Even more preferably, the fetal growth restriction is a reduction in the number of live births.

[0021] More preferably, the adverse pregnancy outcome is decreased disc weight.

[0022] The present invention also claims that the use of chemokine XCL1 in the preparation of a drug for alleviating fetal growth restriction has the following beneficial effects compared with the prior art:

[0023] The present invention discloses the application of chemokine XCL1 in preventing adverse pregnancy outcomes in elderly pregnant women, especially chemokine XCL1 improves growth restriction, indicating its important role in pregnancy. The phenotype of fetal growth restriction in mice can be alleviated by applying XCL1 recombinant protein, reducing the possibility of adverse pregnancy outcomes, and providing a new and effective measure for clinical treatment of adverse pregnancy outcomes in elderly pregnant women in late stages. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 To measure the secretion level of chemokine XCL1 in placental tissue, ELISA kit was used to detect the secretion level of XCL1 in placental tissue of HP and AMA pregnant women or pregnant mice.

[0025] Figure 2 Schematic diagram of the experimental design of the pregnant mouse model. The day when the vaginal plug was found was recorded as P0.5. PBS or chemokine XCL1 recombinant protein was continuously injected through the tail vein for 5 days at P13.5 of pregnancy. The mice were treated at P18.5 of pregnancy to detect the disease phenotype of the fetus.

[0026] Figure 3 is the weight growth rate of the female mice. The figure shows the weight of the female mice recorded at the same time every day and the calculated weight growth rate changes.

[0027] Figure 4 A representative image of a fetus.

[0028] Figure 5 The disease phenotype of the fetus includes fetal weight, placental weight, fetal body length, fetal tail length and number of live fetuses. DETAILED DESCRIPTION

[0029] The present invention is further described in detail below in conjunction with the accompanying drawings and specific examples of the specification. The examples are only used to explain the present invention and are not used to limit the scope of the present invention. The test methods used in the following examples are conventional methods unless otherwise specified; the materials and reagents used are reagents and materials that can be obtained from commercial channels unless otherwise specified.

[0030] Example 1 Secretion level of chemokine XCL1 in placental tissue

[0031] ELISA kit was used to detect the level of chemokine XCL1 secreted by placental tissue of healthy pregnant women (HP) and AMA

[0032] 1. Experimental subjects

[0033] Placental samples of HP and AMA were collected at Nanfang Hospital of Southern Medical University.

[0034] 2. Experimental steps

[0035] The placental tissue was ground, digested, and lysed to obtain a cell suspension, which was resuspended in 1640 medium containing 15% fetal bovine serum, with 0.15×10 cells per well. 6 The cells were plated in a 96-well round-bottom plate and cultured at 37°C for 8 h. The culture supernatant was collected and the secretion level of XCL1 in the supernatant was detected using an ELISA kit (human: DG10426H; mouse: DG30351M, Dogesce).

[0036] 3. Experimental results

[0037] The results are as follows Figure 1 The results showed that compared with HP, the secretion level of XCL1 in AMA placenta was significantly decreased, indicating that the adverse pregnancy outcome of AMA was closely related to the insufficient secretion of chemokine XCL1.

[0038] Example 2 Construction of pregnant mouse model

[0039] 1. Experimental subjects

[0040] C57BL / 6J pregnant mice, 24 to 32 weeks old.

[0041] 2. Experimental design

[0042] like Figure 2 As shown, pregnant mice were injected with XCL1 recombinant protein into the tail vein as the experimental group; pregnant mice in the control group were injected with an equal amount of PBS into the tail vein.

[0043] 3. Experimental steps

[0044] The day when vaginal plugs were detected in mice was recorded as P 0.5. The model was established at P13.5. The experimental group was injected with chemokine XCL1 recombinant protein (R&D system, AF486, 2 μg / day) via tail vein in a volume of 200 μl, and the control group was injected with the same volume of PBS via intraperitoneal injection for 5 consecutive days. The mice were euthanized at P18.5.

[0045] Example 3 Detection of the weight growth rate of mice

[0046] 1. Experimental steps

[0047] In the process of constructing the pregnant mouse model of Example 2, the control pregnant mice and the modeling pregnant mice were recorded as P0.5 on the day when the vaginal plug was detected, and the mouse weight was recorded as W1. Thereafter, the weight of the pregnant mice Wn was recorded at the same time every day until P18.5. The weight growth rate was calculated as (Wn-W1) / W1.

[0048] 2. Experimental results

[0049] The results are as follows Figure 3The results showed that the body weight growth rate of female mice was significantly increased after tail vein injection of chemokine XCL1 recombinant protein compared with the control group.

[0050] Example 4 Detection of fetal disease phenotype

[0051] 1. Experimental steps

[0052] For the control pregnant mice and modeling pregnant mice in Example 2, the female mice were killed by cervical dislocation on P18.5, and the disease phenotypes (fetal weight, placental weight, fetal body length, fetal tail length and number of live fetuses) of the experimental group and the control group were compared.

[0053] 2. Experimental results

[0054] The results are as follows Figure 4 and Figure 5 The results showed that compared with the control group, the fetal weight and placental weight of mice increased after the injection of chemokine XCL1 recombinant protein through the tail vein, and the fetal length, fetal tail length and number of live fetuses increased, suggesting that the administration of recombinant protein XCL1 can alleviate the fetal growth restriction caused by AMA.

[0055] In summary, AMA presents with a phenotype of fetal growth restriction in late pregnancy, and the adverse pregnancy outcome of fetal growth restriction can be significantly alleviated by injecting XCL1 recombinant protein into the tail vein of AMA.

Claims

1. The use of chemokine XCL1 in the preparation of a drug for preventing adverse pregnancy outcomes, characterized in that: The adverse pregnancy outcome is fetal growth restriction in older pregnant women in late pregnancy.

2. The use according to claim 1, characterized in that: The fetal growth restriction refers to a decrease in fetal weight.

3. The use according to claim 1, characterized in that: The fetal growth restriction is caused by decreased placental weight.

4. The use according to claim 1, characterized in that: The fetal growth restriction is a shortening of the fetal body length and / or tail length.

5. The use according to claim 1, characterized in that: The fetal growth restriction is a reduction in the number of live fetuses.

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