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Method for constructing mouse preeclampsia model

A preeclampsia and model technology, applied in the field of biomedicine, can solve the problems of lack of research models, no pregnancy specificity, Gal-9 pathological changes and pathogenesis of preeclampsia, etc.

Pending Publication Date: 2020-08-11
THE OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, on the 8th or 9th day of pregnancy, rats were injected with adenovirus carrying sFlt-1 into the tail vein, and PE-like changes such as blood pressure elevation, proteinuria, and kidney lesions appeared at the end of pregnancy; multiple hypoxia-inducible factor 1α (HIF-1α ) overexpression model has also been applied to the pathogenesis of preeclampsia (PE) oxidative stress; inflammatory response and cytokine stimulation such as LPS or inflammatory factors TNF-α, IL-6 injection of rats can successfully establish preeclampsia (PE) ) models, etc.; however, due to the diversity of PE pathophysiology and clinical manifestations, there is no single animal model that can effectively simulate all the characteristics of preeclampsia (PE), especially the lack of features that can reflect the characteristics of preeclampsia (PE). Preeclampsia (PE) research model of pathological changes and disease progression. In addition, some inducers will also cause hypertension and proteinuria that are not pregnancy-specific when applied during non-pregnancy. Therefore, the application of the model is limited
[0006] Galectin-9 (Gal-9) is a member of the lectin family and is widely expressed in a variety of tissues; so far there has been no research report on the relationship between Gal-9 and the pathological changes and pathogenesis of preeclampsia (PE)

Method used

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  • Method for constructing mouse preeclampsia model
  • Method for constructing mouse preeclampsia model
  • Method for constructing mouse preeclampsia model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0186] Example 1: Pre-eclampsia-related symptoms in pregnant mice induced by injection of recombinant Gal-9

[0187] Animals and diet: C57 / B6 mice of 6-8 weeks were purchased from Slack and raised in the experimental animal room of the Obstetrics and Gynecology Hospital of Fudan University. After adaptation, 80 C57 / B6 female mice with normal estrous cycle were housed with mature male mice of the same strain (2:1), and the vaginal plug was seen in the next morning as the mice were considered to be pregnant for 0.5 days;

[0188] Grouping and treatment of animals: 13 C57 / BL6 female mice on the 8.5th day of pregnancy were randomly divided into 5 mice in the control group (PBS) and 8 mice in the Gal-9 group; 10 non-pregnant C57 / BL6 female mice of the same age were also divided into There were 5 rats in each of the control group (PBS) and the Gal-9 group. Pregnant mice in the Gal-9 group were intraperitoneally injected with recombinant mice Gal-9 200 μg / mouse / day on the 8.5th, 10....

Embodiment 2

[0193] Example 2: Injection of recombinant Gal-9 causes the placenta and fetal mice of pregnant mice to shrink

[0194] Each group of female mice was treated as described in Example 1, and was killed at 18.5 days of pregnancy, the uterus was dissected, and the fetal mice and placenta were stripped; figure 2 As shown in A, the implantation number and embryo absorption rate of pregnant mice were not significantly different between the Gal-9 injection group and the control group. Such as figure 2 As shown in B, the size of the fetal mice and placenta in the Gal-9 injection group was significantly smaller than that of the control group, and the weight of the fetal mice and the wet weight of the placenta were significantly reduced, suggesting that the high expression of Gal-9 leads to restricted embryonic growth and development and poor placental development. combine figure 1 The results indicated that the exogenous administration of Gal-9 could lead to typical symptoms of pree...

Embodiment 3

[0195] Example 3: Experiments of Gal-9 injection causing abnormal decidualization, poor spiral artery remodeling and destruction of placental labyrinth vascularization

[0196] Animals and diet: the same as in Example 1.

[0197] Grouping and treatment of animals: 16 C57 / BL6 female mice on the 8.5th day of pregnancy were randomly divided into 5 mice in the control group (PBS) and 8 mice in the Gal-9 group. Pregnant mice in the Gal-9 group were intraperitoneally injected with recombinant mice Gal-9 200 μg / mouse / day on days 8.5, 10.5, and 12.5 of pregnancy; pregnant mice in the control group were intraperitoneally injected with PBS 200 μl / mouse / day at the corresponding time. The mice were sacrificed on the 12.5th day of pregnancy, the uterus was dissected, the placenta was removed, and a complete pregnancy tissue of the implantation site (including the uterus, placenta, and fetal mouse) was fixed and embedded in paraffin or frozen OCT to prepare paraffin or the preparation of f...

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Abstract

The invention belongs to the field of biomedicines, and relates to a method for constructing a preeclampsia (PE) model and a new purpose of Gal-9 as a biologic marker for preparing a forecast and prognosis assessment platform of PE. Based on characteristic pathological changes as well as etiology and pathogenesis of attack of PE, and based on assessing of clinical manifestation, organ function damaged state and development of embryo placentas, a mouse model most similar to PE clinical indications is constructed and obtained. A quantifying observation index of the model, constructed by the invention, is suitable for researching early nosogenesis of PE, assessing PE onset risk, forecasting prognosis of mothers and children, and assessing curative effect end points before clinical applicationof medicines, and a standard platform is provided for further researching and comparing advantages and disadvantages of different medicines.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a method for constructing an animal model, in particular to a method for constructing a mouse preeclampsia (PE) model, and Galectin-9 (Gal-9) is used as a biomarker for preparing preeclampsia (PE) new uses in the prediction and prognosis evaluation platform. The model established by the present invention is suitable for quantitative index observation and research on preeclampsia (PE), including: early pathogenesis, PE risk assessment, maternal and child prognosis prediction, and drug preclinical efficacy endpoint assessment, etc., and for further research to compare different The advantages and disadvantages of drugs provide a standardized platform. Background technique [0002] The prior art discloses that preeclampsia (PE) is a pregnancy-specific syndrome involving multiple systems and the fetus. In clinical practice, it is mainly characterized by high blood pressure, proteinuria, and ...

Claims

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Application Information

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IPC IPC(8): A61K38/17G01N33/68G01N33/543G01N33/50
CPCA61K38/1732G01N33/5044G01N33/543G01N33/689G01N2800/368
Inventor 杜美蓉李彦虹林懿空李大金
Owner THE OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIV
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