[Expression of ubiquitin-specific protease 7 in lung tissue of preterm rats after hyperoxia exposure].

OBJECTIVE: To study the expression and significance of ubiquitin-specific protease 7 (USP7) and the key factors of the Wnt signaling pathway in the lung tissue of preterm rats after hyperoxia exposure. METHODS: A total of 180 preterm neonatal Wistar rats were randomly divided into an air control group, an air intervention group, a hyperoxia control group, and a hyperoxia intervention group, with 45 rats in each group. Lung injury was induced by hyperoxia exposure in the hyperoxia groups. The preterm rats in the intervention groups were given intraperitoneal injection of the USP7 specific inhibitor P5091 (5 mg/kg) every day. The animals were sacrificed on days 3, 5, and 9 of the experiment to collect lung tissue specimens. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. RT-PCR and Western blot were used to measure the mRNA and protein expression levels of USP7 and the key factors of the Wnt signaling pathway ß-catenin and α-smooth muscle actin (α-SMA) in lung tissue. RESULTS: The air groups had normal morphology and structure of lung tissue; on days 3 and 5, the hyperoxia control group showed obvious alveolar compression and disordered structure, with obvious inflammatory cells, erythrocyte diapedesis, and interstitial edema. On day 9, the hyperoxia control group showed alveolar structural disorder and obvious thickening of the alveolar septa. Compared with the hyperoxia control group at the corresponding time points, the hyperoxia intervention group had significantly alleviated disordered structure, inflammatory cell infiltration, and bleeding in lung tissue. At each time point, the hyperoxia groups had a significantly lower radial alveolar count (RAC) than the corresponding air groups (P < 0.05), and the hyperoxia intervention group had a significantly higher RAC than the hyperoxia control group (P < 0.05). On days 3, 5, and 9 of the experiment, the hyperoxia groups had significantly higher mRNA expression of USP7 and ß-catenin and protein expression of USP7, ß-catenin, and α-SMA than the corresponding air groups (P < 0.05). Compared with the hyperoxia control group, the hyperoxia intervention group had significant reductions in the mRNA expression of ß-catenin and the protein expression of ß-catenin and α-SMA (P < 0.05), while there were no significant differences in the mRNA and protein expression of USP7 between the hyperoxia intervention and hyperoxia control groups (P > 0.05). There were no significant differences in the mRNA expression of USP7 and ß-catenin and the protein expression of USP7, ß-catenin, and α-SMA between the air intervention and air control groups (P > 0.05). CONCLUSIONS: Hyperoxia exposure can activate the Wnt/ß-catenin signaling pathway, and USP7 may participate in hyperoxic lung injury through the Wnt/ß-catenin signaling pathway. The USP7 specific inhibitor P5091 may accelerate the degradation of ß-catenin by enhancing its ubiquitination, reduce lung epithelial-mesenchymal transition, and thus exert a certain protective effect against hyperoxic lung injury.

[Expression of heme oxygenase-1 and inducible nitric oxide synthase in the lungs of hyperoxia-exposed preterm rats].

OBJECTIVE: To study the expression and the role of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) in preterm rats with hyperoxia-induced lung injuries. METHODS: Sixty-four three-day-old preterm Sprague-Dawley rats were randomly assigned to a hyperoxia group (90% oxygen exposure) and a control group (room air exposure), with 32 rats in each group. After 3 days or 7 days of exposure, the lung activity of HO-1 and nitric oxide (NO) contents in bronchoalveolar lavage fluid (BALF), pulmonary histopathologic changes, and the cellular distribution and expression of HO-1 and iNOS in the lungs were measured. RESULTS: After 3 days and 7 days of exposure, the hyperoxia group showed acute lung injuries characterized by the presence of hyperaemia, red cell extravasation and inflammatory infiltration. The NO contents in BALF and the iNOS expression in the lungs increased significantly in the hyperoxia group compared with those in the control group 3 and 7 days after exposure. The expression of HO-1 in macrophages in the lungs increased significantly in the hyperoxia group compared with that in the control group 3 and 7 days after exposure. The NO contents in BALF and the iNOS and HO-1 expression in the lungs increased significantly 7 days after hyperoxia exposure compared with 3 days after hyperoxia exposure. CONCLUSIONS: iNOS and HO-1 levels in the lungs increase in preterm rats with hyperoxia-induced lung injuries, suggesting that iNOS and HO-1 may play roles in hyperoxia-induced pulmonary injuries.