罗氟司特减轻肺炎链球菌肺炎大鼠的肺损伤  

Roflumilast alleviates lung injury in rats with pneumococcal pneumonia

作　　者：黄黎芳[1] 李艳钰 蔺曜 黄瑶[3] HUANG Lifang;LI Yanyu;LIN Yao;HUANG Yao(Pharmacy Department,Affiliated Hospital of Sichuan Health and Rehabilitation Vocational College,the Fourth People′s Hospital of Zigong City,Zigong 643000;Health Management Center,Chengdu Wenjiang District People′s Hospital,Chengdu 611135,China;Department of Pathology,Chengdu Wenjiang District People′s Hospital,Chengdu 611135,China)

机构地区：[1]自贡市第四人民医院/四川卫生康复职业学院附属医院药剂科,四川自贡643000 [2]成都市温江区人民医院健康管理中心,四川成都611135 [3]成都市温江区人民医院病理科,四川成都611135

出　　处：《基础医学与临床》2024年第10期1400-1406,共7页Basic and Clinical Medicine

基　　金：自贡市科技计划项目(2021ZC)。

摘　　要：目的探究罗氟司特对肺炎链球菌(SP)诱导的肺炎大鼠肺损伤的影响。方法将大鼠随机分为对照(control)组、肺炎模型(model)组、罗氟司特低和高剂量组以及罗氟司特高剂量+Colivelin组(STAT3激活剂)干预模型组。检测PaO_(2)、PaCO_(2)、IL-1β、IL-8、IL-10、TNF-α水平;肺组织湿/干比(W/D值)、MDA含量、MPO和SOD活性;HE染色观察肺组织病理损伤;检测肺组织细胞凋亡、cleaved caspase-3、IL-6、p-STAT3/STAT3蛋白表达。结果与对照组相比,模型组大鼠肺组织有明显损伤;血液PaO_(2)、氧合指数(OI)、肺组织IL-10水平、SOD活性显著降低,血液PaCO_(2)水平、肺组织IL-1β、IL-8、TNF-α水平、W/D值、MDA含量、MPO活性、细胞凋亡率、cleaved caspase-3、IL-6、p-STAT3/STAT3蛋白水平升高(P<0.05)。与模型组相比,罗氟司特低、高剂量组大鼠肺组织损伤显著减轻;血液PaO_(2)、OI值、肺组织IL-10水平、SOD活性显著升高,血液PaCO_(2)水平、肺组织IL-1β、IL-8、TNF-α水平、W/D值、MDA含量、MPO活性、细胞凋亡率、cleaved caspase-3、IL-6、p-STAT3/STAT3蛋白表达水平显著降低(P<0.05);Colivelin可部分逆转罗氟司特对SP肺炎大鼠肺损伤的改善作用(P<0.05)。结论罗氟司特可降低SP诱导的肺炎大鼠炎性反应、氧化损伤和细胞凋亡,改善肺功能。Objective To investigate the effect of roflumilast on pulmonary injury induced by Streptococcus pneumonia(SP)in rat model.Methods Rats were randomly divided into control group,pneumonia model group,roflumilast low dose group,high dose group and roflumilast high dose plus Colivelin(STAT3 activator)intervention group.The level of PaO_(2),PaCO_(2),IL-1β,IL-8,IL-10 and TNF-αwere detected.Lung tissue wet/dry ratio(W/D),MDA content,MPO and SOD activity were examined.HE staining microscopy was used to observe the pathological injury of lung tissue.Apoptosis,cleaved caspase-3,IL-6,and p-STAT3/STAT3 protein expression were detected.Results Compared with the control group,the lung tissue of animals in the model group showed obvious damage;blood PaO_(2),oxygenation index(OI),lung tissue IL-10 level,and SOD activity were all significantly reduced;the level of blood PaCO_(2),lung tissue IL-1β,IL-8,TNF-αand W/D values,MDA content,MPO activity,cell apoptosis rate,cleaved caspase-3,IL-6,and p-STAT3/STAT3 protein expression were significantly increased(P<0.05).Compared with the model group,the lung tissue damage of rats in the low and high dose groups of roflumilast was obviously reduced;the level of blood PaO_(2),OI and,lung tissue IL-10,and SOD activity were obviously increased,the level of blood PaCO_(2),lung tissue IL-1β,IL-8,TNF-αand,W/D values,MDA content,MPO activity,cell apoptosis rate,cleaved caspase-3,IL-6,and p-STAT3/STAT3 protein expression were significantly reduced(P<0.05);Colivelin was able to partially reverse the improvement effect of roflumilast on lung injury in rats with SP pneumonia(P<0.05).Conclusions Roflumilast may inhibit inflammatory response,oxidative damage and apoptosis of SP-induced pneumonia in rats resulting in an improvement of lung function.

关 键 词：罗氟司特 肺炎链球菌 肺炎 肺损伤 

分 类 号：R563.1[医药卫生—呼吸系统]