Progress in animal model research on obstructive sleep apnea

doi:10.3969/j.issn.1674-8115.2024.04.011

Abstract

Abstract:

Obstructive sleep apnea (OSA) is a common sleep disorder, and its pathophysiological mechanism complex and not fully understood. This article elaborately explores three categories of OSA animal models: natural, direct and indirect, emphasizing their advantages and disadvantages in simulating OSA pathophysiological processes. Natural OSA models primarily focus on spontaneous upper airway obstructions. Direct OSA models induce OSA through direct obstruction of the airway, while indirect OSA models mainly investigate the impacts of chronic intermittent hypoxia (IH) and sleep deprivation (SD) on the organism. Although these models have played a pivotal role in studying the pathophysiological mechanisms of OSA and developing new therapeutic methods, they also present certain limitations and challenges. Future research directions include the development of non-invasive monitoring technologies, establishing OSA-combined models, and the application of gene-editing technologies, aiming to more comprehensively and accurately simulate the complexity and diversity of human OSA, providing more insights into its mechanisms and developing new therapeutic methods.

Key words: obstructive sleep apnea, intermittent hypoxia, sleep deprivation, animal model

CLC Number:

R562.1

SHEN Yubin, OU Xiwen, LIU Song. Progress in animal model research on obstructive sleep apnea[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(4): 501-508.

Figures/Tables 1

TrendMD

References 30

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Classification	Name	Advantage	Limitation	Applicable scenario
Natural OSA animal model	Obese pigs, English bulldogs, Obese Zucker rats, New Zealand Obese mice	No intervention required; closer to actual conditions	Difficult to fully control variables, adjust research conditions, and cover features closely related to unique human lifestyles and environmental factors	Studying the physiological, genetic, metabolic impacts and the long-term effects of chronic OSA
Direct OSA animal model	OSA animal model with tracheal intubation	Consistently inducing the same degree of upper airway narrowing; easy to control the frequency and duration of apnea events	Technical difficulty and high cost; invasive models are prone to stress responses, and the airway obstruction plane differs from humans	Studying the acute physiological effects of short-term OSA; not suitable for large-scale studies
	OSA animal model of airway collapse induced by negative pressure	Simple, stable, and repeatable operation; no need for complex surgeries or equipment	Unable to stably induce the same degree of upper airway collapse	Researching the chronic impacts of long-term OSA, such as the development of cardiovascular diseases
	OSA animal model with filling material injection	Relatively simple operation; spontaneous chronic IH pathophysiological changes occur; imaging can be used as support	Animals show individual differences, poor repeatability; potential for injection site infections	Studying the effects of anatomical and functional changes in the upper airway on OSA
	Chemically induced OSA animal model	Minimally invasive, few surgery-related complications; high repeatability	High technical requirements and complexity in operation; requiring precise and skilled experimental techniques and high-end experimental equipment	Researching the pathophysiological characteristics of OSA during specific sleep stages
	Special mask ventilation blockage method, Head-enclosed ventilation blockage method, oral-nasal airbag ventilation blockage method	Controllable ventilation and occlusion times	High equipment requirements; difficult operation; insufficient precision in control; restricting animal free movement	Not suitable for more complex or larger-scale studies
Indirect OSA animal model	Chronic IH model	No anesthesia required; non-invasive; precise control of gas concentrations within the chamber; safe and repeatable modeling process	Unable to simulate upper airway narrowing or collapse; CO₂ partial pressure changes do not match actual conditions	Suitable for mechanistic research, long-term studies, and large-scale physiological and pharmacological research
Indirect OSA animal model	Sleep deprivation model	Ability to adjust the intensity and duration of sleep deprivation as needed; facilitating a repeatable process	Introduction of additional stress factors; possibility of leading to a certain degree of exercise deprivation effect, confinement, and fixation stress	Researching the impact of decreased sleep quality and disordered sleep structure on cognitive function, learning and memory, emotional regulation, and metabolic diseases in OSA, and the treatment effects of improving sleep quality on these diseases

Classification	Name	Advantage	Limitation	Applicable scenario
Natural OSA animal model	Obese pigs, English bulldogs, Obese Zucker rats, New Zealand Obese mice	No intervention required; closer to actual conditions	Difficult to fully control variables, adjust research conditions, and cover features closely related to unique human lifestyles and environmental factors	Studying the physiological, genetic, metabolic impacts and the long-term effects of chronic OSA
Direct OSA animal model	OSA animal model with tracheal intubation	Consistently inducing the same degree of upper airway narrowing; easy to control the frequency and duration of apnea events	Technical difficulty and high cost; invasive models are prone to stress responses, and the airway obstruction plane differs from humans	Studying the acute physiological effects of short-term OSA; not suitable for large-scale studies
	OSA animal model of airway collapse induced by negative pressure	Simple, stable, and repeatable operation; no need for complex surgeries or equipment	Unable to stably induce the same degree of upper airway collapse	Researching the chronic impacts of long-term OSA, such as the development of cardiovascular diseases
	OSA animal model with filling material injection	Relatively simple operation; spontaneous chronic IH pathophysiological changes occur; imaging can be used as support	Animals show individual differences, poor repeatability; potential for injection site infections	Studying the effects of anatomical and functional changes in the upper airway on OSA
	Chemically induced OSA animal model	Minimally invasive, few surgery-related complications; high repeatability	High technical requirements and complexity in operation; requiring precise and skilled experimental techniques and high-end experimental equipment	Researching the pathophysiological characteristics of OSA during specific sleep stages
	Special mask ventilation blockage method, Head-enclosed ventilation blockage method, oral-nasal airbag ventilation blockage method	Controllable ventilation and occlusion times	High equipment requirements; difficult operation; insufficient precision in control; restricting animal free movement	Not suitable for more complex or larger-scale studies
Indirect OSA animal model	Chronic IH model	No anesthesia required; non-invasive; precise control of gas concentrations within the chamber; safe and repeatable modeling process	Unable to simulate upper airway narrowing or collapse; CO₂ partial pressure changes do not match actual conditions	Suitable for mechanistic research, long-term studies, and large-scale physiological and pharmacological research
Indirect OSA animal model	Sleep deprivation model	Ability to adjust the intensity and duration of sleep deprivation as needed; facilitating a repeatable process	Introduction of additional stress factors; possibility of leading to a certain degree of exercise deprivation effect, confinement, and fixation stress	Researching the impact of decreased sleep quality and disordered sleep structure on cognitive function, learning and memory, emotional regulation, and metabolic diseases in OSA, and the treatment effects of improving sleep quality on these diseases

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