A Silicosis Mouse Model Established by Repeated Inhalation of Crystalline Silica Dust

Hangbing Cao; Bing Li; Haoming Chen; Yehong Zhao; Yuanjie Zou; Yang Liu; Min Mu; Xinrong Tao

doi:10.3791/64862

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Method Article

A Silicosis Mouse Model Established by Repeated Inhalation of Crystalline Silica Dust

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DOI:

10.3791/64862

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January 6th, 2023

Hangbing Cao^*¹^,²^,³^,⁴ , Bing Li^*¹^,²^,³^,⁴ , Haoming Chen¹^,³^,⁴ , Yehong Zhao¹^,⁴ , Yuanjie Zou¹^,⁴ , Yang Liu¹^,⁴ , Min Mu¹^,²^,³^,⁴ , Xinrong Tao¹^,²^,³^,⁴

¹Key Laboratory of Industrial Dust Control and Occupational Health of the Ministry of Education, Anhui University of Science and Technology, ²Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Anhui University of Science and Technology, ³Anhui Province Engineering Laboratory of Occupational Health and Safety, ⁴School of Medicine, Department of Medical Frontier Experimental Center, Anhui University of Science and Technology

^* These authors contributed equally

Summary

This protocol describes a method for establishing a mouse model of silicosis through repeated exposure to silica suspensions via a nasal drip. This model can efficiently, conveniently, and flexibly mimic the pathological process of human silicosis with high repeatability and economy.

Abstract

Silicosis can be caused by exposure to respiratory crystalline silica dust (CSD) in an industrial environment. The pathophysiology, screening, and treatment of silicosis in humans have all been extensively studied using the mouse silicosis model. By repeatedly making mice inhale CSD into their lungs, the mice can mimic the clinical symptoms of human silicosis. This methodology is practical and efficient in terms of time and output and does not cause mechanical injury to the upper respiratory tract due to surgery. Furthermore, this model can successfully mimic acute/chronic transformation process of silicosis. The main procedures were as follows. The sterilized 1-5 µm CSD powder was fully ground, suspended in saline, and dispersed in an ultrasonic water bath for 30 min. Mice under isoflurane-induced anesthesia switched from shallow rapid breathing to deep, slow aspiration for approximately 2 s. The mouse was placed in the palm of a hand, and the thumb tip gently touched the lip edge of the mouse's jaw to straighten the airway. After each exhalation, the mice breathed in the silica suspension drop by drop through one nostril, completing the process within 4-8 s. After the mice's breathing had stabilized, their chest was stroked and caressed to prevent the inhaled CSD from being coughed up. The mice were then returned to the cage. In conclusion, this model can quantify CSD along the typical physiological passage of tiny particles into the lung, from the upper respiratory tract to the terminal bronchioles and alveoli. It can also replicate the recurrent exposure of employees due to work. The model can be performed by one person and does not need expensive equipment. It conveniently and effectively simulates the disease features of human silicosis with high repeatability.

Introduction

Workers are inevitably exposed to irregular crystalline silica dust (CSD), which can be inhaled and is more toxic in numerous occupational contexts, including mining, pottery, glass, quartz processing, and concrete¹^,². A chronic dust inhalation condition known as silicosis causes progressive lung fibrosis³. According to epidemiological data, the incidence of silicosis has been declining globally over the past few decades, but in recent years, it has been increasing and affecting younger people⁴^,⁵^,⁶