Effect of ulinastatin on hyperoxia-induced acute lung injury in infantile rats: relationship with Wnt/β-catenin signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of ulinastatin on hyperoxia-induced acute lung injury (ALI) and its relationship with Wnt/β-catenin signaling pathway in infantile rats.Methods:A total of 36 clean-grade Sprague-Dawley rats, aged 14 days, weighing 40-50 g, were divided into 3 groups ( n=12 each) control group (C group), hyperoxia-induced ALI group (ALI group) and ulinastatin group (UTI group). Hyperoxia-induced ALI was induced by inhaling oxygen at concentration greater than 90% for 72 h. At 1 day after the model was established successfully, ulinastatin 50 000 U/kg was injected intraperitoneally daily at the same time for 3 consecutive days in group UTI, while the equal volume of normal saline was injected intraperitoneally at the same time point in C and ALI groups.The animals were sacrificed at 4 days after the model was established successfully, the lung tissues were taken for determination of the wet/dry weight ratio (W/D ratio), for microscopic examination of the pathological changes which were scored, for measurement of interleukin-6 (IL-6) IL-1β and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and for detection of the expression of phosphorylated glycogen synthase kinase (p-GSK-3β), Wnt3a and β-catenin by Western blot, and ultrastructure was examined with with an electron microscope. Results:Compared with C group, W/D ratio and lung injury score were significantly increased, the contents of IL-6, IL-1β and TNF-α were increased, and the expression of p-GSK-3β, Wnt3a and β-catenin were up-regulated in lung tissues in group ALI ( P<0.05). Compared with group ALI, W/D ratio and lung injury score were significantly decreased, the contents of IL-6, IL-1β and TNF-α were decreased, and the expression of p-GSK-3β, Wnt3a and β-catenin were down-regulated in lung tissues in group UTI ( P<0.05). The ultrastructure injury in group UTI was reduced as compared with group ALI. Conclusion:The mechanism by which ulinastatin can alleviate hyperoxia-induced ALI is related to inhibiting the activation of Wnt/β-catenin signaling pathway and decreasing inflammatory response in infantile rats.