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Construction method and application of non-alcoholic steatohepatitis mouse model based on PEDF/ApoE double-gene knockout

A steatohepatitis, non-alcoholic technology, applied in the medical field, can solve the problems of evaluation, inability to simultaneously simulate the pathological characteristics and disadvantages of NASH pathogenesis, and achieve the effect of simple and easy method.

Pending Publication Date: 2022-06-24
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

None of the current animal models of NASH can simultaneously simulate the onset characteristics, pathogenesis process and pathological characteristics of each stage of NASH
It is particularly noteworthy that the current NASH animal models have a common problem, that is, the inflammatory response is mild, and it is difficult to induce severe liver inflammatory response
Severe hepatic inflammatory response is precisely a significant sign that distinguishes NASH from simple fatty liver. Obviously, the current NASH animal model is not conducive to the evaluation of preclinical drug effects

Method used

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  • Construction method and application of non-alcoholic steatohepatitis mouse model based on PEDF/ApoE double-gene knockout
  • Construction method and application of non-alcoholic steatohepatitis mouse model based on PEDF/ApoE double-gene knockout
  • Construction method and application of non-alcoholic steatohepatitis mouse model based on PEDF/ApoE double-gene knockout

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Animal body weight, blood lipid content, serum insulin content and blood glucose were measured.

[0029] At the 24th week of induction, the animals in the above four groups were fasted for 12-16 hours, weighed, and blood glucose was measured by a blood glucose meter, and the mice were dissected to collect serum samples, and commercial kits were used to detect serum total cholesterol, triglyceride and insulin levels. , the result is figure 1 shown, wherein A: body weight; B: serum total cholesterol content; C: serum total triglyceride content; D: serum insulin content; F: blood glucose; **, p<0.01, vs wild normal group; ***, p<0.001, vs. wild-type normal group; ##, p<0.01, vs. wild-type high-fat group; ###, p<0.001, vs. wild-type high-fat group; &, p<0.05, vs. ApoE knockout high-fat group; &&& , p<0.001, vs ApoE knockout high-fat group.

[0030] Nonalcoholic steatohepatitis is often associated with obesity, dyslipidemia, insulin resistance, and hyperglycemia, figure 1...

Embodiment 2

[0032] The above-mentioned four groups of animals were evaluated for liver weight, liver-to-body ratio, liver function enzyme levels, liver steatosis, liver inflammation and liver fibrosis at 24 weeks of induction.

[0033] At the 24th week of induction, animals were fasted for 12-16 hours and then sacrificed by anesthesia. Serum and tissue samples were collected, and liver tissue was weighed; serum alanine aminotransferase and aspartate aminotransferase levels were detected using commercial kits; Sections were stained with HE and Masson to evaluate liver lesions. The results are as follows figure 2As shown, where A: liver weight; B: liver body ratio; C: serum alanine aminotransferase level; D: serum aspartate aminotransferase level; E: HE staining; F: CD45 immunohistochemical staining; G: liver steatosis score; H: liver ballooning lesion score; I: liver lobular inflammation score; J: Masson staining; K: liver fibrosis score; *, p<0.05, vs wild-type normal group; **, p<0.01, ...

Embodiment 3

[0038] The number of liver tumors in the above four groups of animals was counted and the tumors were identified when the animals were induced for 24 weeks.

[0039] At the 24th week of induction, animals were fasted for 12 hours and then sacrificed by anesthesia. Serum and tissue samples were collected, and the number of mice that died and developed liver tumors in each group was counted. Paraffin sections were stained with HE and immunohistochemical staining of AFP, PCNA, and CD31 to further clarify tumor lesions. The results are as follows: image 3 As shown in the figure, where A: statistics of tumor occurrence; B: PET / CT results of tumor mice; C: general picture of tumor tissue (after fixation); D: HE staining of tumor tissue; E: AFP staining of tumor tissue; F: tumor tissue PCNA immunohistochemistry; G: tumor tissue CD31 immunohistochemistry.

[0040] Some patients with nonalcoholic steatohepatitis will develop into hepatocellular carcinoma, showing the characteristics ...

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Abstract

The invention discloses a construction method and application of a non-alcoholic steatohepatitis mouse model based on PEDF / ApoE double-gene knockout, and belongs to the technical field of medicine. According to the model, a PEDF / ApoE double-gene knockout mouse is induced by a high-fat feed to generate a non-alcoholic steatohepatitis phenotype, and the model is simple and convenient in construction method and easy to popularize. The mouse model constructed by using the method provided by the invention can better simulate the lesion characteristics of human non-alcoholic steatohepatitis, especially has extremely strong liver inflammatory response and liver fibrosis phenotypes, and has a certain probability of developing into liver tumors; therefore, the compound has important application prospect and value in the field of research and development of drugs for metabolic diseases such as non-alcoholic steatohepatitis.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for constructing a mouse model of nonalcoholic steatohepatitis based on PEDF / ApoE double gene knockout and its application. Background technique [0002] Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by steatosis and lipid storage in liver cells without a history of excessive alcohol consumption. It has become the main cause of chronic liver disease worldwide. The pathological changes include simple fatty liver, non-alcoholic steatohepatitis (NASH), liver fibrosis, and eventually develop into liver cirrhosis and hepatocellular carcinoma with the progression of the disease. NASH is an extreme form of nonalcoholic fatty liver development, defined as the appearance of steatosis accompanied by inflammation and liver cell damage, and is characterized by liver steatosis, inflammation, liver cell damage, and varying degree...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01K67/02A61K49/00
CPCA01K67/02A61K49/0008A01K2267/0362A01K2227/105
Inventor 蔡卫斌李兴会
Owner SUN YAT SEN UNIV
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