Rapamycin prevents lung injury related to acute spinal cord injury in rats

Scientific Reports, 2023 · DOI: 10.1038/s41598-023-37884-6 · Published: July 5, 2023

Simple Explanation

This study investigates how rapamycin, a drug that activates autophagy, affects lung damage after acute spinal cord injury (ASCI) in rats. The research aims to find new ways to prevent lung injury following ASCI by regulating autophagy. The study found that rapamycin pretreatment reduced lung damage, such as cell death and inflammation, in rats after ASCI. It also increased the levels of certain proteins (Beclin1, LC3, and RAB7) that indicate autophagy is occurring. The researchers suggest that rapamycin protects against lung injury after ASCI by enhancing autophagy through the AMPK–mTORC1–ULK1 regulatory axis, a key pathway in cellular function.

Study Duration

72 hours

Participants

144 female wild-type Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
Rapamycin pretreatment significantly reduced lung damage after ASCI, including cell death, inflammatory exudation, hemorrhage, and pulmonary congestion, at 12 and 48 hours post-injury.
2
Rapamycin pretreatment increased the levels of key autophagy markers (Beclin1, LC3, and RAB7) in the lungs after ASCI, indicating enhanced autophagy induction.
3
Rapamycin's protective effect on lung injury after ASCI is possibly mediated through the upregulation of autophagy via the AMPK–mTORC1–ULK1 regulatory axis.

Research Summary

This study investigates the potential protective effects of rapamycin, an autophagy activator, on lung injury following acute spinal cord injury (ASCI) in rats. The researchers hypothesized that rapamycin-induced autophagy could mitigate lung damage post-ASCI. The study found that rapamycin pretreatment reduced lung damage, decreased cell apoptosis, and increased autophagy markers in the lungs of rats after ASCI. These effects were observed through gross anatomy, lung pathology, apoptosis assessment, and autophagy induction analysis. The researchers concluded that rapamycin can prevent lung injury after ASCI, potentially by upregulating autophagy through the AMPK–mTORC1–ULK1 regulatory axis. This provides a new theoretical basis for preventing lung injury post-ASCI.

Practical Implications

Therapeutic Potential

Rapamycin may be a potential therapeutic agent to prevent or reduce lung injury following acute spinal cord injury.

Targeted Intervention

The AMPK-mTORC1-ULK1 regulatory axis can be further explored as a target for therapeutic interventions aimed at mitigating lung injury post-ASCI.

Clinical Application

The study supports the clinical use of rapamycin to prevent and treat ASCI-induced lung injury.

Study Limitations

1
The study was conducted on female rats, and the results may not be generalizable to males.
2
The precise molecular mechanisms underlying the protective effects of rapamycin on lung injury after ASCI require further investigation.
3
The long-term effects of rapamycin pretreatment on lung function and overall outcomes after ASCI were not evaluated.

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