Construction methods and uses of animal models simulating the characteristics of various hfrs diseases

An animal model and construction method technology, applied in pharmaceutical formulations, compound screening/testing, preparations for in vivo testing, etc., can solve the problems of mouse nervous system lesions, inability to simulate well, inconsistent characteristics, etc.

Active Publication Date: 2022-07-26
FOURTH MILITARY MEDICAL UNIVERSITY
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Problems solved by technology

Although it was clear in the 1950s that neonatal mice inoculated with HTNV can cause fatal diseases, but it mainly causes neurological lesions in mice, which is inconsistent with the characteristics of HFRS disease, so it has limitations.
In addition, the SCID mice reported in the previous literature can be used as an evaluation system for HTNV-infected animals, based on the fact that high levels of virus-specific antigens can be detected in the mouse liver, spleen, and lung after virus infection, and liver, spleen, and lung tissues There were obvious pathological changes in the brain, but no obvious pathological changes in the heart, brain, and kidney tissues. However, this SCID mouse model cannot well simulate the main disease characteristics of HFRS: acute renal injury and thrombocytopenia, has certain restrictions

Method used

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  • Construction methods and uses of animal models simulating the characteristics of various hfrs diseases
  • Construction methods and uses of animal models simulating the characteristics of various hfrs diseases
  • Construction methods and uses of animal models simulating the characteristics of various hfrs diseases

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Embodiment 1

[0025] 1. Experimental materials

[0026] (1) HTNV 76-118 strain: HTNV strain is 76-118 strain (international standard strain), which was donated by researcher Hang Changshou of Chinese Center for Disease Control and Prevention, and later preserved and amplified by our laboratory. Vero-E6 cells were infected with HTNV after intoxication in the brain of suckling mice, and the titer of the virus amplified in Vero-E6 cells was used in this study.

[0027] (2) C57BL / 6WT and NLRC3 KO mice: 6-8 weeks old, purchased from Shanghai Southern Model Biology Co., Ltd.

[0028] 2. Experimental method

[0029] (1) Infection experiment of NLRC3 KO mice

[0030] NLRC3 KO mice were infected by intraperitoneal injection of HTNV 76-118 virus, and the infection dose was 5×105PFUs / 50μL / mice, which was recorded as the experimental group, and the uninfected mice were recorded as the control group.

[0031] The body temperature and body weight of the mice were continuously monitored every day after...

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Abstract

The present invention relates to a method for constructing an animal model, in particular to a method for constructing an animal model for simulating the characteristics of various HFRS diseases and its use. The method is to infect NLRC3KO mice by intraperitoneal injection of HTNV 76-118 virus, and the infection dose is 5×10 5 PFUs / 50μL / mouse; the characteristics of the disease are: diffuse renal tubular dilatation in the model mice, renal medullary capillary hemorrhage; a large number of extramedullary hematopoietic foci in the spleen, edema, degeneration and necrosis of hepatocytes in the liver; The number of platelets decreased, the number of white blood cells decreased, and the liver and kidney function were damaged at the same time. The animal model constructed by the present invention can be used for the screening and efficacy evaluation of HFRS disease drugs.

Description

technical field [0001] The present invention relates to a method for constructing an animal model, in particular to a method for constructing an animal model simulating the characteristics of various HFRS diseases and its use. Background technique [0002] Hantavirus (Hantavirus) belongs to the genus Orthohantavirus of the family Hantaviridae of the order Buniavirus. The segment encodes viral RNA-dependent RNA polymerase (RNA-dependent RNA polymerase), the middle (M) segment encodes viral envelope glycoproteins (Gn and Gc), and the small (S) segment encodes viral nucleoprotein (NP) . Humans are mainly infected with Hantavirus through contact with the excrement of its natural host (rodent) or by direct bite, which mainly causes two serious diseases, namely hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HPS). HFRS is a natural foci disease characterized by fever, hemorrhage, and acute renal impairment. [0003] The natural host of HTN...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A01K67/027A61K49/00
CPCA61K35/76A61K49/0008A01K67/027A01K2267/0337
Inventor 吴兴安刘蓉蓉马瑞雪刘梓谕侯诗源王芳应旗康张晓晓
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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