Asthma

Whole Body Plethysmography (WBP)

Introduction

Asthma is generally considered as a disease with the characteristics of chronic airway inflammation, airway hyper-responsiveness and remodeling. Multiple cells are involved in its onset. Airway epithelium directly contact with allergens and is involved in the onset of the asthma, which is possibly colsely connect to the asthma, chronic airway inflammation, and airway remodeling. Airway hyper-responsiveness (AHR) is the reversible airflow obstruction caused by various pharmacological, chemical and physical factors, which is an important indicator for therapeutic effect of asthma.

The whole body plethysmography (WBP) is used for monitoring respiratory function and airway hyper-responsiveness of experimental animals in the state of conscious and free movement, without restraint and anesthesia. It avoid the impact of traumatic tracheostomy and anesthesia, and the animals survived after the experiment, it is an ideal experimental method for long-term tracking research. It can test multiple animals simultaneously and is the best choice for screening experiments.

The WBP system can be used for asthma researches and is particularly suitable for high throughput and long-term tracking researches such as primary drug screening, analysis of pharmacological efficacy and toxicology. The respiratory rate, tidal volume, peak expiratory volume, peak inspiratory volume and intensified breathing intervals (Penh) which indirectly represents the airway resistance measured by this system are highly correlated with results of classical lung function tests.

Material and Modeling Methods

Materials:

Aluminum hydroxide, ovalbumin, acetylcholine (0, 3.125, 6.25, 12.5, 25, 50mg/mL);

Experimental animals: BALB/c (clean grade 6-8 weeks), male, 20 ± 2g;

Positive drug: Dexamethasone; Experimental drugs;

Whole Body Plethysmography (WBP, TOW-INT Tech).

Modeling:

For 8 consecutive weeks, subcutaneous injection of allergenic solution will be performed on Mondays of each week (allergenic solution ratio: 100ug of OVA+20ug of

AL (OH) 3; Dissolved in 200ul of physiological saline), blank group injects the equal volume of physiological saline;

One week after the 8th injection, start atomizing with a 5% OVA solution for 45 minutes per day for 10 consecutive days. The blank group was atomized with physiological saline of equal volume and time.

Bronchial Provocation Test - Airway Hyper-responsiveness Test

Before the official start of the experiment, the mice were placed in the WBP test chamber three times for adaptation, each mice adapts for 30-60 minutes per time.

During the experiment, the mice were placed in a whole body plethysmography and adapts for 5 minutes. Then, one by one, nebulize Mch from 0 to 50mg/mL for stimulation, and the animals rest for 10 minutes after simulation of each concentration, perform Penh analysis on the collected data after experiment.

Penh Explanation:

Penh is an indicator for quantifying the degree of bronchial constriction: an indicator for quantifying the scalability of the bronchi and trachea, which is also known as the expiratory interval value. Penh is an unitless calculated value that reflects airway resistance.

The method for calculating the percentage change in Penh is: (Penh value stimulated by Mch - Penh value stimulated by NS) / Penh value stimulated by NSx100%.

Conclusion

During the application of Mch in bronchial stimulation tests, as the concentration of Mch increases, both the mice of the normal control group and the model group gradually showed open mouth breathing, slowed breathing, deepened amplitude and appearance of abdominal breathing, along with changes in respiratory waveforms which are more significant in the model group mice (Figure 2). After the stimulation test, Penh, EF50, Vt, and Pause values in the lung function measurement values of the model group mice showed a significant increase compared to the normal control group mice, while other values were not significant. Normal control group mice were compared before and after stimulation with Mch, the Penh, EF50, Pause, and PEF values significantly increased, while other lung function measurement values showed no significant changes.

The whole body plethysmography system (WBP) is convenient and effective to use, and can continuously detect and observe the process of dynamic changes. Can be applied to large-scale animal experiments and drug screening, especially suitable for detection of changes in lung function in chronic lung disease model animals which requires the tacking research. The Penh value shows a good dose-response relationship when detecting the hyper-responsiveness of mouse asthma model induced by Mch, it is an indicator of animal lung function that can effectively reflect AHR.

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