Objective: To explore the effects and mechanism of narciclasine on hyperoxia-induced acute lung injury in neonatal rats. Methods: A total of 40 full-term neonatal Wistar rats were randomly divided into the normoxia group (21% O2)

normoxia+narciclasine group

hyperoxia group (85% O2

hyperoxia) and hyperoxia+narciclasine group

with 10 cases in each group. Rats in all groups were exposed under conditions of different oxygen contents for 7 d. Other 50 full-term neonatal rats were randomly divided into the normoxia group

hyperoxia group

hyperxia+narciclasine group

hyperoxia+narciclasine+protein kinase B (AKT) inhibitor group and hyperoxia+narciclasine+rapamycin group

with 10 cases in each group. All drug therapy groups were intraperitoneally injected with 1 mg/kg narciclasine

1 mg/kg AKT inhibitor and 4 mg/kg rapamycin at 0

2

4 and 6 d after birth

respectively. The levels of lung injury

pro-inflammatory cytokines

fibrosis and lung tissue apoptosis among all groups were compared. Results: Compared with the normoxia group

body mass and levels of B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) in lung tissues decreased significantly in the hyperoxia group

total number of cells in bronchoalveolar lavage fluid (BALF)

total protein

wet and dry weight of lung tissues

levels of tumor necrosis factor α (TNF-α)

interleukin-1β (IL-1β)

monocyte chemotactic protein 1 (MCP-1) and IL-6 in BALF and serum

expressions of α smooth actin (α-SMA)

vimentin and collagen Ⅰ in lung tissues

apoptosis rate of lung tissues

fibroblast apoptosis rate of primary lung

phosphorylated protein kinase B (p-AKT)/AKT and phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR increased significantly (P<0.05)

and there was no significant change in the above indicators between the normoxia group and the normoxia+narciclasine group (P>0.05). Compared with the hyperoxia group

body mass and Bcl-2/Bax levels in lung tissues increased significantly in the hyperoxia+narciclasine group

total number of cells in BALF

total protein

wet and dry weight of lung tissues

levels of TNF-α

IL-1β

MCP-1 and IL-6 in BALF and serum

expressions of α-SMA

vimentin and collagen Ⅰ in lung tissues

apoptosis rate of lung tissues

fibroblast apoptosis rate of primary lung

p-AKT/AKT and p-mTOR/mTOR decreased significantly (P<0.05). Compared with the hyperoxia+narciclasine group

levels of TNF-α and IL-1β increased significantly in the hyperoxia+narciclasine+AKT inhibitor group (P<0.05)

levels of TNF-α

IL-1β and expressions of collagen Ⅰ increased significantly in the hyperoxia+narciclasine+rapamycin group

and the levels of Bcl-2/Bax decreased significantly (P<0.05). Conclusion: Narciclasine can protect neonatal rats from hyperoxia-induced lung injury. The mechanism may be related to that narciclasine can activate AKT/mTOR signaling pathways

improve the inflammation response

relieve the lung fibrosis and inhibit the apoptosis of lung tissues.