Expression of ubiquitin-specific protease 7 in lung tissue of preterm rats after hyperoxia exposure / 中国当代儿科杂志

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 β-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 (@*CONCLUSIONS@#Hyperoxia exposure can activate the Wnt/β-catenin signaling pathway, and USP7 may participate in hyperoxic lung injury through the Wnt/β-catenin signaling pathway. The USP7 specific inhibitor P5091 may accelerate the degradation of β-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 / 中国当代儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Influence of Heme Oxygenase-1 Inhibitor Protoporphyrin Ⅸ Zinc on Hyperoxic Lung Injury in Preterm Rats / 实用儿科临床杂志

Objective To explore the effect of protoporphyrin Ⅸ zinc(Znpp) on hyperoxic lung injury in preterm rats.Methods Three-day-old preterm SD rats were randomly assigned to room air control group(group Ⅰ)hyperoxia control group(oxygen≥900 mL/L)(group Ⅱ),room air plus Znpp group(group Ⅲ),hyperoxia plus Znpp group(group Ⅳ).Group Ⅲ and group Ⅳ were injected intraperitoneally with ZnPP 45 ?mol/kg each day.After the third day and the 7th day of exposure,the activity of heme oxygenase-1(HO-1) and the percent of carboxyhemoglobin(HbCO) in the lungs,the lung wet weight /dry weight ratio(W/D),tumor necrosis factor-?(TNF-?),total protein and malondialdehyde(MDA) in bronchoalveolar lavage fluid were determined and lung histophathological changes were examined in all groups.Results On the third day,compared with group Ⅰ the activity of HO-1 and the percent of HbCO in the lungs,W/D,TNF-?,total protein and MDA,all greatly rised in group Ⅱ(Pa

Changes of Expression and Activity of Heme Oxygenase-1 in Lung Tissue of Hyperoxia-Induced Preterm Rats / 实用儿科临床杂志

Objective To observe the changes of expression and activity of heme oxygenase-1(HO-1) in lung tissue of preterm rats exposed to hyperoxia,and explore the role of HO-1 in hyperexia-induced lung injury of preterm rats.Methods Three-day-old preterm rats of standard SD were randomly assigned to hyperoxia group and air group.At the third and 7th day of exposure,the expressions of HO-1 mRNA were detected by means of reverse transcription polymerase chain reaction and the cellular distribution and expressions of HO-1 protein in the lung were measured by immunohistochemical techniques,respectivesly,and the active of HO-1 was determined also.Results On the third day,in air group,the expressions of HO-1 mRNA(0.17 ?0.08),HO-1(7.23?4.63)were mildly expressed and the activity of HO-1 was(4.32?1.57) nmol/(mg?h);compared with those of air group,the expression of HO-1 mRNA in hyperoxia group(0.72?0.33) was significantly increased(Pa