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

作　　者：郑立风 张露 赵红霞 李芳圆 梁金排 Zheng Lifeng;Zhang Lu;Zhao Hongxia;Li Fangyuan;Liang Jinpai(Hengshui People's Hospital,Hengshui 053000;Shenzhou City Hospital,Shenzhou 053000,China)

机构地区：[1]衡水市人民医院呼吸与危重症科,衡水053000 [2]深州市医院呼吸与危重症科,深州053000

出　　处：《解剖学杂志》2023年第5期395-400,427,共7页Chinese Journal of Anatomy

基　　金：河北省卫健委医学科学研究项目(20191786)。

摘　　要：目的:探究不同吸氧浓度对慢性阻塞性肺病(COPD)大鼠环加氧酶2(COX-2)/前列腺素(PGE)/E-前列腺素类激素(EP)信号通路及上皮细胞活性的作用机制。方法:将大鼠随机分为正常对照组、COPD组、50%O_(2)组、70%O_(2)组、90%O_(2)组。检测大鼠肺功能;ELISA法检测肺泡灌洗液(BALF)中PGE2、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平;计算巨噬细胞、中性粒细胞和淋巴细胞百分比;H-E染色观察肺组织病理学变化;免疫印迹检测肺组织中COX-2、EP1、EP4蛋白表达。将BEAS-2B细胞分为对照组、香烟烟雾提取物(CSE)组、50%O_(2)组、70%O_(2)组、90%O_(2)组,CCK-8法和流式细胞仪检测BEAS-2B细胞增殖和凋亡能力。结果:与正常对照组相比,COPD组大鼠肺功能指标吸气阻力(RI)、肺总量(TLC)均增加,50 ms用力呼气量(FEV_(50))/用力肺活量(FVC)比值明显降低;与COPD组相比,50%O_(2)组和70%O_(2)组大鼠肺功能指标TLC、RI均明显降低,FEV_(50)/FVC比值明显升高,且70%O_(2)组肺功能指标变化最显著;与COPD组相比,90%O_(2)组大鼠肺功能指标TLC、RI均明显增加,FEV_(50)/FVC比值明显降低。与正常对照组相比,COPD组大鼠BALF中IL-6、IL-8、TNF-α、PGE2水平、白细胞总数及单核-巨噬细胞、淋巴细胞、中性粒细胞比例均明显升高;与COPD组相比,50%O_(2)组和70%O_(2)组大鼠BALF中IL-6、IL-8、TNF-α、PGE2水平、白细胞总数及单核-巨噬细胞、淋巴细胞、中性粒细胞比例均明显降低,且70%O_(2)组降低最显著;与COPD组相比,90%O_(2)组大鼠BALF中IL-6、IL-8、TNF-α、PGE2水平、白细胞总数及单核-巨噬细胞、淋巴细胞、中性粒细胞比例明显升高。与正常对照组相比,COPD组大鼠肺组织中COX-2、EP1、EP4蛋白表达均明显增加;50%O_(2)组和70%O_(2)组大鼠肺组织中COX-2、EP1、EP4蛋白表达明显低于COPD组;与COPD组相比,90%O_(2)组大鼠肺组织中COX-2、EP1、EP4蛋白表达均明显增加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)%O_(2) group,70%O_(2) group,and 90%O_(2) 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)%O_(2) group,70%O_(2) group,and 90%O_(2) 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(FEV_(50))to forced vital capacity(FVC).Compared with the COPD group,rats in the _(50)%O_(2) and 70%O_(2) groups showed significantly decreased TLC and RI,along with a significant increase in the FEV_(50)/FVC ratio.The 70%O_(2) group exhibited the most significant changes in lung function.In contrast,the 90%O_(2) group showed significantly increased TLC and RI,as well as a significant decrease in the FEV_(50)/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

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 

分 类 号：R563.9[医药卫生—呼吸系统] R-332[医药卫生—内科学]