To investigate adenoviral vector mediated exogenous gene expression in mouse lungs and the effect of mIFN γ transgene expression on allergen induced pulmonary eosinophil infiltration in a murine asthmatic model Methods LacZ marker gene was transduced into CD 1 mouse airway epithelial cells by installation of a replication deficient adenovirus with LacZ gene (AdCMVLacZ) 5×10 9 plaque forming unit (pfu) in the intratrachea or nostril C57 mice were sensitized intraperitoneally and challenged by aerosol with ovalbumin (OVA) to produce an asthmatic model AdCMVmIFNγ 5×10 9 pfu was administered via nostril in asthmatic mice 48 h before OVA challenge Sera, bronchial alveolar lavage (BAL) and lungs were recovered 48 h after OVA challenge Results After administration with AdCMVLacZ by intratracheal installation or nose drop, the lungs revealed a high level of widespread LacZ transduction with X gal staining, mainly along airways IFN γ via adenoviral vector transduction could be overexpressed both in vitro and in vivo (1624 7±1321 5 pg/ml in BAL 96 h after AdCMVIFNγ infection) In AdCMVIFNγ treated asthmatic models, histological evaluation revealed marked suppression of eosinophil peribronchial and perivascular infiltration; the recoverable percentage of eosinophils in BAL was an average of 9 00%±4 58%, which was a statistically significant decrease versus that of the positive control group (75 13%±6 85%) ( P <0 001) The total cell number in BAL ((145±55 6)×10 3 cells/ml) in AdCMVmIFNγ treated mice also was tremendously reduced compared to the positive control group ((216 6±71 1)×10 3 cells/ml) Conclusions Adenoviral vector was able to overexpress exogenous gene in murine lungs IFN γ overexpression via adenoviral vector in pulmonary epithelia in vivo can abrogate allergen induced eosinophilic infiltration in lungs in an asthmatic model, which may suggest a new preventively therapeutic method for cytokine immunogenetic transfer in allergic asthma
背景与目的肺癌是慢性阻塞性肺疾病(慢阻肺)重要的合并症,会显著影响慢阻肺患者的预后。慢阻肺也会影响肺癌患者的术后并发症和复发。本研究旨在调查胸外科住院肺癌合并慢阻肺的情况。方法回顾性分析北京大学人民医院胸外科2015年1月-2015年12月收治的原发性非小细胞肺癌患者。通过查阅病历获取患者的性别、年龄、吸烟状况、有害职业史、症状、胸部计算机断层扫描(computed tomography,CT)、术后病理、出院诊断、全套肺功能及支气管舒张试验,当基础肺功能第一秒钟用力呼气容积(forced expiratory volume in one second,FEV_1)占预计值<70%时即行支气管舒张试验。结果 703例肺癌患者进行了全套肺功能测定,其中67例进行支气管舒张试验,62例(92.5%)符合慢阻肺诊断。接受手术治疗的肺癌患者有677例,其中41例进行支气管舒张试验,38例(92.7%)符合慢阻肺诊断。在接受手术治疗的肺癌患者中合并慢阻肺者年龄≥65岁、男性、有吸烟史和非腺癌的比例高于未合并慢阻肺者,差异有统计学意义(P<0.05);男性和≥65岁者更易合并慢阻肺(OR:2.807-2.374,95%CI:1.101-7.157)(P<0.05)。住院前仅有3例(4.3‰)诊断慢阻肺并按慢阻肺规范治疗。出院时仅有5例(7.1‰)诊断慢阻肺。结论在胸外科住院肺癌患者中行常规肺功能及支气管舒张试验可提高肺癌合并慢阻肺的诊断;当前肺癌合并慢阻肺诊断和治疗严重不足,需要引起胸外科医生重视,与呼吸内科医生携手共同防治慢阻肺。
