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Establishment of fulminant liver function failure model of rhesus

A liver failure, explosive technology, used in organic active ingredients, preparations for in vivo testing, medical preparations containing active ingredients, etc., can solve the problems of toxicity, huge differences in animal survival time, and high costs

Inactive Publication Date: 2012-07-04
WEST CHINA HOSPITAL SICHUAN UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These drug-induced FHF models all have various defects, such as acetaminophen, which has poor reproducibility, and the survival time of animals varies greatly under the same dose; it is accompanied by methemoglobinemia, refractory anemia and other organ damage
D-Galactosamine has poor reproducibility (mortality and time to death vary greatly); high cost (1-2g / kg), not suitable for application in large animals
Thioacetamide (TAA) can easily lead to severe hypotension, hypoglycemia, hypothermia, and renal failure, and can directly cause nerve damage, which is indistinguishable from hepatic encephalopathy; it is highly toxic to experimenters
Viruses can also induce FHF, but their replication is difficult and their biological safety is poor
[0006] Surgical resection of all or most of the liver, or complete defluidization, can also establish the HFH model, but due to the time-consuming operation, large trauma, and large hemodynamic interference; unless the liver is transplanted in situ, the animal cannot survive; the liver itself not damaged
There is no report on the establishment of FHF animal models with large primates

Method used

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  • Establishment of fulminant liver function failure model of rhesus
  • Establishment of fulminant liver function failure model of rhesus
  • Establishment of fulminant liver function failure model of rhesus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] The preparation of embodiment 1 animal model of the present invention

[0030] 1. Materials and methods:

[0031] 1.1 Experimental materials

[0032] Three 3-4-year-old female and male rhesus monkeys, free from herpes B virus, simian retrovirus, simian leukemia virus and immunodeficiency virus infection; purchased from Chengdu Pingan Animal Breeding Base.

[0033] 1.2 Main reagents

[0034] Amanitin (α-amanitin) was purchased from Switzerland Alexis Biochemicals company;

[0035]Endotoxin lipopolysaccharide (LPS) was purchased from SigmaAldrich, USA.

[0036] Other medicines and consumables were purchased from Likang Pharmacy of West China Hospital.

[0037] 1.3 Preparation of the main solution

[0038] Preparation of Abotin solution:

[0039] Solution A: Take the original 1mg / carton of amanitine powder, add 5ml of normal saline to dissolve it, and use it as a storage solution for short-term storage at 4°C.

[0040] Liquid B: According to the weight of the monkey...

Embodiment 2

[0116] Example 2 Utilize the rhesus macaque fulminant hepatic failure animal model of the present invention to evaluate the tissue engineering liver support system or the effect of liver cell and stem cell transplantation and establish a related evaluation system

[0117] a, prepare the rhesus monkey fulminant hepatic failure model according to the method of Example 1, it is to apply abotin in conjunction with lipopolysaccharide endotoxin to primates, and the administration dose of abotin is: 0.1mg / kg, the dose of lipopolysaccharide endotoxin is 1 μg / kg;

[0118] b. Using cell transplantation or organ transplantation in the animal model;

[0119] c. Observe the effect of the quantified indexes of the liver function of the animals after transplantation, and evaluate the effect of the tissue engineering liver support system or the transplantation of liver cells and stem cells.

[0120] After the evaluation in step c, if the liver function index of the transplanted animal is si...

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PUM

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Abstract

The invention provides preparation of an animal model for screening hepatocyte growth-promoting regenerative medicines in fulminant liver function failure curing process and evaluating therapeutic effect of a tissue engineering liver supporting system or hepatic cell and stem cell transplantation by using amanitin and endotoxin lipopoly-saccharide, wherein an application method adopts single intraperitoneal instillation with dosage of 0.1mg / kg, and the dosage of the endotoxin is 1mug / kg. The invention further provides a method for preparing fulminant liver function failure and a fulminant liver function failure animal model prepared by the method. The animal model can be used for evaluation of biotechnological new drugs that a rodent animal model cannot accomplish, and can be used for the evaluation of tissue engineering liver, biological artificial liver, the hepatic cell and stem cell transplantation treatment technologies.

Description

technical field [0001] The invention relates to a method for preparing a rhesus monkey fulminant liver failure model. Background technique [0002] Acute hepatic failure (fulminant hepatic failure, FHF) is common clinically and is mostly caused by viral infection, extensive liver tissue resection, acute drug or poison injury, etc. The prognosis of the patient is dire, and the mortality rate is very high. There is no better way to treat it than liver transplantation. Limited by the severe shortage of donor organs, cell transplantation (mature liver cell or stem cell transplantation), bioartificial liver, tissue engineered liver, etc. have become current research hotspots, but their effectiveness is mostly in small animals (basically rats). obtained on Promoting liver cell regeneration is also a current research hotspot, but satisfactory progress has not been made, and an ideal drug that can significantly promote liver cell regeneration in a short period of time has not yet...

Claims

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Application Information

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IPC IPC(8): A61K31/407A61K31/739A61K49/00A61P1/16
Inventor 石毓君步宏周萍张杰夏杰郭岗李宏霞王莉
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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