解剖学杂志2023，Vol.46Issue(5)：395-400,427,7.DOI:10.3969/j.issn.1001-1633.2023.05.006
不同吸氧浓度对慢性阻塞性肺疾病大鼠环加氧酶2/前列腺素/E-前列腺素类激素信号通路及上皮细胞活性的作用机制
Mechanisms of different oxygen inhalation concentrations on cyclooxygenase-2/prostaglandin E/E-prostanoid signaling and epithelial cell activity in rats with chronic obstructive pulmonary disease
摘要
Abstract
Objective:To investigate the mechanism of action of different oxygen concentrations on cyclooxygenase-2(COX-2)/prostaglandin E(PGE)/E-prostanoid(EP)signaling and epithelial cell activity in chronic obstructive pulmonary disease(COPD)rats.Methods:The rats were randomly divided into the following groups:normal control group,COPD group,50%O2 group,70%O2 group,and 90%O2 group.Lung function of the rats was assessed.ELISA method was used to measure the levels of PGE2,interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α)in the bronchoalveolar lavage fluid(BALF).The percentages of macrophages,neutrophils,and lymphocytes were calculated.H-E staining was performed to evaluate the pathological changes in lung tissue.Immunoblotting was conducted to detect the protein expression of COX-2,EP1,and EP4 in lung tissue.BEAS-2B cells were divided into control group,cigarette smoke extract(CSE)group,50%O2 group,70%O2 group,and 90%O2 group.Cell proliferation and apoptosis ability of BEAS-2B cells were assessed using CCK-8 assay and flow cytometry.Results:Compared with the normal control group,rats in the COPD group exhibited increased inspiratory resistance(RI)and total lung capacity(TLC),as well as a significant decrease in the ratio of forced expiratory volume in 50 milliseconds(FEV50)to forced vital capacity(FVC).Compared with the COPD group,rats in the 50%O2 and 70%O2 groups showed significantly decreased TLC and RI,along with a significant increase in the FEV50/FVC ratio.The 70%O2 group exhibited the most significant changes in lung function.In contrast,the 90%O2 group showed significantly increased TLC and RI,as well as a significant decrease in the FEV50/FVC ratio compared with the COPD group.Compared to the normal control group,rats in the COPD group had significantly elevated levels of IL-6,IL-8,TNF-α,and PGE2 in BALF,along with increased total white blood cell count and percentages of monocyte-macrophages,lymphocytes,and neutrophils.In comparison,the 50%O2 and 70%O2 groups showed significantly decreased levels of IL-6,IL-8,TNF-α,and PGE2 in BALF,as well as reduced total white blood cell count and percentages of monocyte-macrophages,lymphocytes,and neutrophils.The 70%O2 group exhibited the most significant reductions.However,the 90%O2 group showed significantly increased levels of IL-6,IL-8,TNF-α,and PGE2 in BALF,along with increased total white blood cell count and percentages of monocyte-macrophages,lymphocytes,and neutrophils compared with the COPD group.Compared with the normal control group,rats in the COPD group showed significantly increased protein expression of COX-2,EP1,and EP4 in lung tissue.However,the 50%O2 and 70%O2 groups exhibited significantly lower protein expression of COX-2,EP1,and EP4 in lung tissue compared with the COPD group.In contrast,the 90%O2 group showed significantly increased protein expression of COX-2,EP1,and EP4 in lung tissue compared with the COPD group.In the CSE group,BEAS-2B cell viability was lower and apoptosis rate was higher compared with the control group.However,the 50%O2 and 70%O2 groups showed significantly increased cell viability and decreased apoptosis rate compared with the CSE group.On the other hand,the 90%O2 group showed significantly decreased cell viability and increased apoptosis rate compared with the CSE group.Conclusion:In COPD rats,oxygen therapy at concentration of 50%and 70%can inhibit the activation of the COX-2/PEG2/EP signaling pathway,improve lung function,reduce pulmonary infiltration,and increase epithelial cell activity.The best therapeutic effect is observed with a concentration of 70%oxygen.Therapy at a concentration of 90%excerbates pulmonary inflammation in COPD rats,decreases epithelial cell activity and promotes the activation of the COX-2/PEG2/EP signaling pathway.关键词
肺/吸氧浓度/慢性阻塞性肺疾病/环加氧酶2/前列腺素/E-前列腺素类激素信号通路/上皮细胞/增殖/凋亡Key words
lung/oxygen inhalation concentrations/chronic obstructive pulmonary disease/cyclooxygenase-2/prostaglandin E/E-prostanoid signaling/epithelial cell/proliferation/apoptosis引用本文复制引用
郑立风,张露,赵红霞,李芳圆,梁金排..不同吸氧浓度对慢性阻塞性肺疾病大鼠环加氧酶2/前列腺素/E-前列腺素类激素信号通路及上皮细胞活性的作用机制[J].解剖学杂志,2023,46(5):395-400,427,7.基金项目
河北省卫健委医学科学研究项目(20191786) （20191786）
