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Establishing method and application of asthma-like chronic obstructive pulmonary overlap airway inflammation mouse model

A technology of airway inflammation and mouse model, applied in the field of medical biology research, can solve the problems of different types, emphasis on inflammation types, and inconformity with the natural pathogenesis of ACO patients

Active Publication Date: 2020-10-27
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, neither OVA nor PPE is a natural pathogenic factor for asthma and emphysema / COPD, and the model has the following shortcomings: ①Although OVA is a classic method for asthma models, it must be stimulated by intranasal instillation of OVA in mice. The model can be successfully modeled by intraperitoneal injection of OVA sensitization, which is different from the pathogenesis of asthma patients who directly inhale air sensitizers; ②The pan-lobular emphysema model caused by acute alveolar injury caused by one-time instillation of elastase is also consistent with Inconsistent pathological changes of centrilobular emphysema induced by common long-term smoking stimulation in COPD patients
Therefore, the above modeling methods do not conform to the natural pathogenesis of ACO patients, resulting in the extremely limited application of the current ACO model
[0004] In addition, although many studies have focused on the mechanism of smoking on asthma models, there are few animal experiments on the combination of long-term smoke inhalation and asthma allergens, mainly because the following problems are difficult to solve: ①Asthma and emphysema The type of inflammation in COPD is emphasized. When mice inhale cigarettes and allergens at the same time, it is easy to cause the disappearance of the characteristics of the two diseases, which is not a simple superimposed treatment; When the inhaled allergen is active fungal spores, it is more likely to cause sudden death of mice; ③During the experiment, the detection of airway hyperresponsiveness requires the injection of anesthesia drugs and is an invasive operation, and the mice cannot be revived after the routine detection , unable to perform long-term dynamic detection

Method used

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  • Establishing method and application of asthma-like chronic obstructive pulmonary overlap airway inflammation mouse model
  • Establishing method and application of asthma-like chronic obstructive pulmonary overlap airway inflammation mouse model
  • Establishing method and application of asthma-like chronic obstructive pulmonary overlap airway inflammation mouse model

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] 1.1 Model construction (smoking and PAM-induced ACO model)

[0056] A. Experimental animals and grouping

[0057] Twenty SPF-grade C56BL / 6 female mice, aged 4-6 weeks, weighing 16-20 g, were kept in an SPF-grade animal room. The mice were randomly divided into 4 groups (n=5), respectively negative control group (Negative Control; NC group), simple asthma group (PAM group), simple emphysema group (Smoke group) and overlapping group (Smoke+ PAM group), the specific operation steps are as follows:

[0058] ACO-like model induced by smoking (Smoke) and Aspergillus protease (PAM):

[0059] (a) Class ACO group (Smoke+PAM) (such as figure 1 shown):

[0060] ① Smoking treatment: The mice inhaled 4 cigarettes smoke per day from day 0 (about 5 minutes per cigarette, with an interval of 10 minutes between each cigarette), 5 days a week (no smoking treatment for the remaining 2 days of the week, and normal feeding was completed). Yes), a total of 120 days. In order to simulat...

Embodiment 2

[0101] 2.1 Model construction (nCB and PAM-induced ACO model)

[0102] A. Experimental animals and grouping

[0103] Twenty SPF-grade C57BL / 6 female mice, aged 6-8 weeks, weighing 16-20 g, were raised in an SPF-grade animal room. Mice were randomly divided into 4 groups (n=5), negative control group (NC group), pure asthma group (PAM group), simple emphysema group (nCB group) and overlapping group (nCB+PAM group) , the specific operation steps are as follows:

[0104] 15nm nano-carbon black particles (Nanoparticulate carbon black, nCB) (Cabot Corporation, Monarch 1100 [4] and a PAM-induced ACO-like model:

[0105] (a) Class ACO group (nCB+PAM) (such as Figure 5 shown):

[0106] ①nCB treatment: mice were intranasally instilled with nCB (50 μg / mouse) every other day from day 0, three times a week for a total of 4 weeks, and then rested for 4 weeks;

[0107] ②Allergen treatment: mice were sensitized with intranasal drops of PAM (9 μg / mouse) every other day from day 43 (all...

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Abstract

The invention discloses an establishing method and application of an asthma-like chronic obstructive pulmonary overlap airway inflammation mouse model. The model is constructed by any one of the following modes: S1, smoking and aspergillus protease induced ACO-like model: enabling mice to inhale smoke of cigarettes every day from the 0th day; after smoking treatment is completed for 3-7 days, enabling an aspergillus protease solution to be dropwise added into the noses to sensitize the mice, wherein an ACO-like model is constructed; S2, preparing an ACO-like model induced by nano carbon blackparticles and aspergillus protease: intranasally dripping the nano carbon black particles into the anesthetized mice from the 0th day, wherein after the nano carbon black particles are treated for 2 weeks, an aspergillus protease solution is dropwise added into the noses to sensitize mice, and an ACO-like model is constructed. The constructed ACO-like model can simulate the characteristic that asthma chronic obstructive pulmonary overlap occurs in the later stage of diseases of patients with chronic obstructive pulmonary disease clinically, and an experimental animal model is provided for ACOmorbidity mechanism and drug treatment research.

Description

technical field [0001] The invention belongs to the field of medical biology research, and in particular relates to a method for establishing a mouse model of asthma-like COPD overlapping airway inflammation and its application. Background technique [0002] Asthma-COPD overlap (ACO) is a disease state clinically characterized by both asthma and chronic obstructive pulmonary disease (COPD), and the incidence rate in obstructive airway diseases is about 20% . Global Asthma Report [1] It is pointed out that compared with simple asthma or COPD, the lung function of ACO patients declines faster and the condition worsens more frequently, and has become one of the major diseases with high disability and mortality rates in the world. However, most clinical studies of asthma and COPD exclude patients with ACO features due to the heterogeneity and uncertainty of chronic airway inflammation and the lack of knowledge about ACO. Moreover, most of the current clinical research on ACO ...

Claims

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Application Information

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IPC IPC(8): A01K67/027A61K49/00
CPCA01K67/027A01K2207/20A01K2207/35A01K2227/105A01K2267/0368A61K49/0008
Inventor 曾智敏郭禹标黄鑫炎曾宇莹陈凤佳谭卫平
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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