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Fetal-derived adult cholestatic liver injury animal model, its specific biomarkers and its application

A technology of cholestasis and animal models, applied in biochemical equipment and methods, compound screening/testing, preparations for in vivo experiments, etc., to achieve high repeatability, easy promotion and application, and easy operation

Active Publication Date: 2021-10-22
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the application of dexamethasone during pregnancy has a "double-edged sword" effect

Method used

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  • Fetal-derived adult cholestatic liver injury animal model, its specific biomarkers and its application
  • Fetal-derived adult cholestatic liver injury animal model, its specific biomarkers and its application
  • Fetal-derived adult cholestatic liver injury animal model, its specific biomarkers and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] [Example 1] Construction of an animal model of fetal-derived adult cholestatic liver injury

[0035] Proceed as follows:

[0036] 1. Animals and Handling

[0037] 20 male Wistar rats (body weight 260-300g), and 40 female Wistar rats (body weight 200-240g). Provided by Hubei Provincial Animal Center. Free to drink and eat, after 7 days of adaptive feeding, according to male: female = 1:2 cage, vaginal smear in the next morning, to determine the pregnant rats, recorded as pregnancy 0 day. The pregnant rats were randomly divided into two groups: the control group and the prenatal dexamethasone exposure (PDE) group, and the experimental group (PDE group) pregnant rats were treated with 0.2 mg / kg.d dexamethasone subcutaneously from GD9 to GD20. Injection treatment, while the control group was given the same volume of saline. Some pregnant mice were sacrificed on the 20th day of pregnancy to take the livers of the fetuses, and the relevant indicators of liver bile acid me...

Embodiment 2

[0063] [Example 2] Using the animal model of the present invention to screen for therapeutic drugs for fetal-derived adult cholestatic liver injury

[0064] Proceed as follows:

[0065] 1. Construct an animal model of fetal-derived adult cholestatic liver injury according to the method steps of Example 1;

[0066] 2. Give nilvadipine drug treatment to the fetal-derived adult cholestatic liver injury animal model constructed in step 1:

[0067] Select the female offspring of the PDE group, give the CYP27A1 activity inhibitor Nilvadipine (Nilvadipine) 1.4mg / kg.d from 8 weeks to 12 weeks after birth, and detect the effect of Nilvadipine on the cholestasis of the PDE group female offspring rats at 28 weeks effects of liver injury. The experiment was divided into four groups: the control group, which was not exposed to dexamethasone and given the same volume of normal saline; the PDE group; the Nilvadipine treatment group, which was given Nilvadipine drug intervention in the PDE ...

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Abstract

The invention provides an animal model of fetal-derived adult cholestatic liver injury, its specific biomarker and application. The animal model is constructed using the following method steps: take normally pregnant mice / mice, and give 0.2 mg / kg.d dexamethasone subcutaneously during the 9-20 days of pregnancy; the pregnant mice naturally produce F1 offspring, Select litters with a litter size ≥ 10, and retain 10 litters per litter, with half males and half females. After breastfeeding for 4 weeks, the litters are weaned, and the males and females are kept in separate cages to continue feeding with a normal diet; take a normal diet until the age of 28 weeks The related indexes of serum and liver cholestatic liver injury were detected, and the increase of related indexes was judged as the occurrence of fetal-derived adult cholestatic liver injury. The animal model of fetal cholestatic liver injury is of great significance for studying the mechanism of fetal cholestatic liver injury in adults, determining its toxicity targets, and developing early prevention and treatment drugs.

Description

technical field [0001] The invention relates to the technical field of animal model construction, in particular to an animal model of fetal-derived adult cholestatic liver injury, its specific biomarkers and applications. Background technique [0002] It is known that cholestasis occurs due to abnormal bile metabolism or disturbance of bile flow, which can lead to liver damage, even fibrosis, cirrhosis. Hydrophobic bile acids mainly include cholic acid (CA), chenodeoxycholic acid (CDCA) and muricholic acid (MCA), etc., and their accumulation in liver cells is considered to be a symptom of cholestatic liver disease. important inducing factor for injury. Endoplasmic reticulum stress has been confirmed to be one of the main pathogenesis of adult cholestatic liver injury. Bile acids can induce mitochondrial damage and endoplasmic reticulum stress in hepatocytes by increasing glucose-regulated protein 78 (GRP78). C / EBP homologous protein (CCAT / enhancer-binding homologues prote...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A01K67/027A61K49/00C12N9/02
CPCA01K67/0275A01K2207/20A01K2227/105A01K2267/03A61K49/0008C12N9/0073
Inventor 汪晖郭喻胡文张棋路小倩
Owner WUHAN UNIV
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