Journal
SPINE JOURNAL
Volume 18, Issue 5, Pages 845-856Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.spinee.2018.01.001
Keywords
Acute spinal cord injury; Autophagy; Beclin 1; LC3; Lung; P62
Categories
Funding
- Natural Science Foundation of China (NSFC) [81272172]
- National Key Specialty Construction of Clinical Projects of China [2013-544]
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BACKGROUND CONTEXT: Lung injury is a major cause of respiratory complications following an acute spinal cord injury (ASCI), which are associated with a high mortality rate. Autophagy has been shown to be involved in a variety of lung diseases; however, whether autophagy is activated in the lung following ASCI remains unknown. PURPOSE: The objective of this study was to investigate the induction of autophagy in the lung after ASCI. STUDY DESIGN: This is an experimental animal study of ASCI investigating kinetics of autophagy in the lung following ASCI. METHODS: One hundred and forty-four rats (N=144) were divided into two groups: (1) a sham (n=72) and (2) an injury group (n=72). Allen's method was used to induce an injury at the level of the 10th thoracic vertebra. Rats were sacrificed at 6, 12, 24, 48, and 72 hours, 1 week, and 2 weeks after surgery. Lung pathology and apoptosis were assessed to determine the level of damage in the lung. LC3, RAB7, P62, and Beclin 1 were used to detect the induction of autophagy. The study was funded by the Natural Science Foundation of China (NSFC, 81272172); National Key Specialty Construction of Clinical Projects of China (#2013-544). The funder of the present study had no capacity to influence the scholarly conduct of the research, interpretation of results, or dissemination of study outcomes. RESULTS: In the injury group, pathologic changes (i.e., pulmonary congestion, hemorrhage, inflammatory exudation, and alveolar collapse) occurred within the lung tissue within 72 hours after ASCI. Apoptosis of the lung cells gradually increased and peaked 72 hours after ASCI. Within 24 hours of ASCI, LC3 expression decreased, recovered, and gradually increased from 24 hours to 72 hours. As RAB7 decreased, P62 increased, and the ratio of RAB7/LC3 significantly decreased. CONCLUSIONS: After ASCI, autophagy in the injured lung underwent dynamic changes, as early autophagosome formation decreased and late autophagosomes accumulated; thus, autophagy is in a state of inhibition. (C) 2018 Elsevier Inc. All rights reserved.
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