Abstract
Severe injury occurs in the lung after acute spinal cord injury (ASCI) and autophagy is inhibited. However, rapamycin-activated autophagy's role and mechanism in lung injury development after ASCI is unknown. Preventing lung injury after ASCI by regulating autophagy is currently a valuable and unknown area. Herein, we aimed to investigate the effect and possible mechanism of rapamycin-activated autophagy on lung damage post-ASCI. An experimental animal study of rapamycin's effect and mechanism on lung damage after ASCI. We randomly divided 144 female wild-type Sprague-Dawley rats into a vehicle sham group (n = 36), a vehicle injury group (n = 36), a rapamycin sham group (n = 36), and a rapamycin injury group (n = 36). The spine was injured at the tenth thoracic vertebra using Allen's method. At 12, 24, 48, and 72 h after surgery, the rats were killed humanely. Lung damage was evaluated via pulmonary gross anatomy, lung pathology, and apoptosis assessment. Autophagy induction was assessed according to LC3, RAB7, and Beclin 1 levels. ULK-1, ULK-1 Ser555, ULK-1 Ser757, AMPK α and AMPK β1/2 were used to investigate the potential mechanism. After rapamycin pretreatment, the lung showed no obvious damage (e.g., cell death, inflammatory exudation, hemorrhage, and pulmonary congestion) at 12 h and 48 h after injury and Beclin1, LC3 and RAB7 levels increased. After rapamycin pretreatment, ULK-1, ULK-1 Ser555, and ULK-1 Ser757 levels increased at 12 h and 48 h after injury compared with the vehicle group, but they decreased at 12 h after injury compared with the rapamycin sham group. After rapamycin pretreatment, AMPKα levels did not change significantly before and after injury; however, at 48 h after injury, its level was elevated significantly compared with that in the vehicle group. Rapamycin can prevent lung injury after ASCI, possibly via upregulation of autophagy through the AMPK-mTORC1-ULK1 regulatory axis.