PI3K抑制剂对甲型流感病毒FM1感染诱导病毒性肺炎小鼠肺组织中NO生成及炎症反应的影响  

Effect of a PI3K Inhibitor on NO Production and Inflammatory Response in the Lung Tissues of Mice with Viral Pneumonia Induced by Influenza A Virus FM1 Infection

作　　者：杨延龙 涂明利 谢明水 YANG Yanlong;TU Mingli;XIE Mingshui(Suizhou Hospital Affiliated to Hubei Institute of Medicine,Suizhou Central Hospital,Suizhou Suixian People's Hospital,Suizhou 441300,China)

机构地区：[1]湖北医药学院附属随州医院,随州市中心医院,随州市随县人民医院,随州441300

出　　处：《病毒学报》2019年第5期713-720,共8页Chinese Journal of Virology

摘　　要：甲型流感病毒(Influenza A virus,IAV)感染可触发细胞因子风暴,并增加急性呼吸窘迫综合征的发生风险,肺组织内炎症反应的级联放大激活在该过程中起到关键作用。磷脂酰肌醇3-激酶(Phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(Protein kinase B,AKT)信号通路参与细胞炎症反应的调控,刺激内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)的表达,并增加一氧化氮(Nitric oxide,NO)的生成,进而通过NO的活性来增加血管通透性并促进炎症细胞浸润、刺激炎症细胞活化,并分泌大量炎症因子。但PI3K/AKT通路在甲型流感病毒感染所致病毒性肺炎中的作用尚未明确。为研究PI3K抑制剂对IAV FM1感染诱导病毒性肺炎小鼠肺组织中NO生成及炎症反应的影响,选择C57BL/6小鼠并随机分为对照组、H1N1组、LY294002组,H1N1组、LY294002组通过病毒液滴鼻的方式建立IAV感染诱导病毒性肺炎的模型,LY294002组从造模当天开始,给予PI3K抑制剂LY294002腹腔注射、连续7d。比较三组小鼠肺组织HE染色及H1N1病毒拷贝数、PI3K/AKT/eNOS通路表达量、NO及炎症因子含量的差异。结果显示,H1N1组肺组织HE染色出现明显的病理损害且H1N1病毒拷贝数、p-PI3K、p-AKT、eNOS的表达量及NO、IL-1β、IL-6、TNF-α、ICAM-1的含量明显高于对照组(P<0.05);LY294002组肺组织HE染色的病理损害减轻且p-PI3K、p-AKT、eNOS的表达量及NO、IL-1β、IL-6、TNF-α、ICAM-1的含量明显低于H1N1组(P<0.05),H1N1病毒拷贝数与H1N1组比较无显著性差异(P>0.05)。本研究提示,PI3K抑制剂对IAV感染诱导病毒性肺炎小鼠肺组织中NO生成及炎症反应具有抑制作用。Influenza A virus(IAV)infection can trigger cytokine storms and increase the risk of acute respiratory distress syndrome(ARDS). Cascade amplification of inflammatory reactions in lung tissue plays a key role in this process. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signalling pathway participates in the regulation of cellular inflammatory response,stimulates the expression of endothelial nitric oxide synthase(eNOS),and increases the production of nitric oxide(NO). Through the activity of NO,PI3K/AKT signalling pathway can increase vascular permeability,promote the infiltration of inflammatory cells,stimulate the activation of inflammatory cells,and secrete a large number of inflammatory factors. However,the role of PI3K/AKT signalling pathway in virulent pneumonia caused by IAV infection has not been clarified.To study the effects of PI3K inhibitors on NO production and the inflammatory response in the lung tissues of mice with viral pneumonia induced by IAV FM1 infection,C57BL/6 mice were divided randomly into control group,H1N1 group and LY294002 group. The models of viral pneumonia induced by infection with the IAV were established by nasal drops in the latter two groups. The LY294002 group was given the PI3K inhibitor LY294002(i.p.)for 7 days from the day of modeling. Differences of hematoxylin and eosin(H&E)staining,H1N1-virus copy number,expression of the PI3K/AKT/eNOS signalling pathway,NO and inflammatory factors in lung tissues of the three groups of mice were compared. H&E staining showed obvious pathologic damage in the lung tissues of the H1N1 group,and the H1N1-virus copy number,expression of p-PI3K,pAKT,eNOS and contents of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α and intercellular adhesion molecule(ICAM)-1 were significantly higher than those of the control group(P<0.05). HE staining showed pathologic damage to be alleviated in the lung tissues of mice in the LY294002 group,and expression of p-PI3K,p-AKT,eNOS and contents of IL-1β,IL-6,TNF-α,ICAM-1 were significantly

关 键 词：甲型流感病毒(IAV) 磷脂酰肌醇3-激酶(PI3K) 一氧化氮(NO) 炎症反应 肺炎 

分 类 号：R373.1[医药卫生—病原生物学] R511[医药卫生—基础医学]