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Role of the lung in the progression of multiple organ dysfunction syndrome in ageing rat model
Xue-Ping Wang1, Qing-Lei Zhu, Qiao Xue
1Institute of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Background:
Multiple organ dysfunction syndrome in the elderly (MODSE) is a problem with high mortality in the critical care of elderly patients. The pathogenesis of MODSE remains elusive. This study aimed to establish rat models of MODSE and to investigate the pathogenetic mechanism responsible for the development of MODSE in the rat models.
Methods:
Twenty-four-month old rats (elderly) received intravenous injection of lipopolysaccharide (LPS) to induce rat model of MODSE. In the model, we observed the physical responses, biochemical indices changes, histopathological features of vital organs, including lung, liver, heart, and kidney. We also investigated the sequence of individual organ dysfunction and changes of proinflammatory factors. Three-month-old rats, serving as young rat controls, received parallel procedures. Besides, normal saline injection was also performed on elderly and young control rats.
Results:
All rats displayed different degree of physical response after LPS injection, preceded by deterioration of respiratory status. At 6 hours, lung injury was observed, which started earlier than other organ injury that was observed in about 24 hours. Furthermore, all vital organ injury was more severe in elderly rats than in young rats at the same time points. After LPS injection, pulmonary alveolar macrophages apoptosis rate increased obviously, and was more significant in elderly rats ((43.4 ± 8.4)%) than in young rats ((24.2 ± 3.0)%). LPS injection also enhanced tumor necrosis factor a (TNF-a) concentration significantly in these organs. Its peak concentration appeared at 6 hours in lung tissue and at 24 hours in other organs after LPS injection. TNF-a level was higher in elderly rats than in young rats at the same time points. The increase was most significant in lung tissue. After intravenous administration of LPS, toll-like receptor 4 (TLR4) expression in lung tissue was upregulated markedly, and peaked at 6 hours. In contrast, upregulation of TLR4 expression in liver peaked at 24 hours, lagging behind that in the lung.
Conclusion:
Lung is the first and most seriously injured organ in rat model of MODSE and it may play an "initiating" role in the development of MODSE.
Insights
Multiple organ dysfunction syndrome in the elderly (MODSE) is a critical care challenge. This study found that lung injury initiates MODSE in elderly rats, preceding other organ damage and inflammation.
Area of Science:
- Critical care medicine
- Geriatric medicine
- Pathophysiology
Background:
- Multiple organ dysfunction syndrome in the elderly (MODSE) presents a significant challenge in critical care due to high mortality rates.
- The underlying pathogenesis of MODSE remains incompletely understood, necessitating further investigation.
Purpose of the Study:
- To establish rat models of MODSE to elucidate the pathogenetic mechanisms involved in its development.
- To investigate the sequence of organ dysfunction and inflammatory responses in MODSE.
Main Methods:
- Elderly (24-month-old) and young (3-month-old) rats were injected with lipopolysaccharide (LPS) to induce MODSE.
- Observed physical responses, biochemical indices, and histopathological changes in vital organs (lung, liver, heart, kidney).
- Assessed organ-specific inflammatory factor changes and toll-like receptor 4 (TLR4) expression.
Main Results:
- LPS injection induced MODSE, with lung injury appearing earliest (6 hours) and being most severe in elderly rats.
- Pulmonary alveolar macrophage apoptosis and tumor necrosis factor-alpha (TNF-α) levels were significantly elevated, particularly in elderly rats.
- Toll-like receptor 4 (TLR4) expression peaked earlier in the lung (6 hours) compared to other organs (24 hours) following LPS administration.
Conclusions:
- The lung serves as the initial and most severely affected organ in the rat model of MODSE.
- The lung likely plays a critical initiating role in the cascade leading to MODSE development.