摘要
目的 研究奥司他韦对肺炎幼鼠ACE2/Ang(1-7)/Mas受体轴、肺损伤及炎症水平的影响。方法 SPF级SD雄性幼鼠50只随机抽取12只作为健康组,剩余38只幼鼠建立流感病毒模型。建模中意外死亡2只,随机数字表法将建模成功的36只幼鼠分为模型组、奥司他韦组及对照组,每组各12只。健康组与模型组幼鼠常规饲养,奥司他韦组幼鼠给予10 mg/kg奥司他韦灌胃,1次/d,持续5 d;对照组幼鼠经尾静脉注射75 mg/mL阿奇霉素,1次/d,持续1周。另取40只SPF级幼鼠建立病毒性肺炎模型后分为激动剂组、抑制剂组、激动剂+奥司他韦组、抑制剂+奥司他韦组,共诊治7 d,1次/d。ELISA检测各组IL-6、IL-8、TNF-α水平。小动物肺功能检测仪检测各组肺功能指标。HE染色观察各组肺炎幼鼠肺组织病理形态。TUNEL检测各组幼鼠肺组织细胞凋亡。免疫印迹检测各组幼鼠ACE2、Ang(1-7)、MasR、ACE、AngⅡ蛋白表达水平。结果 与健康组相比,模型组、奥司他韦组与对照组幼鼠血清中IL-6、IL-8、TNF-α、肺组织细胞凋亡率升高(P<0.05),在经过奥司他韦干预后IL-6、IL-8、TNF-α、肺组织细胞凋亡率均降低(P<0.05)。与健康组相比,模型组FEF50、FEF75、MMF、PEF水平降低(P<0.05),肺系数升高(P<0.05),在经过奥司他韦干预后FEF50、FEF75、MMF、PEF水平升高(P<0.05),肺系数降低(P<0.05)。各组肺组织病理形态对比明显。与健康组相比,模型组、奥司他韦组、对照组、抑制剂组、激动剂组、激动剂+奥司他韦组与抑制剂+奥司他韦组ACE2、Ang(1-7)、MasR水平降低(P<0.05),ACE、AngⅡ水平升高(P<0.05);与模型组相比,奥司他韦组、对照组、激动剂组、激动剂+奥司他韦组ACE2、Ang(1-7)、MasR水平升高(P<0.05),ACE、AngⅡ水平降低(P<0.05),抑制剂组ACE2、Ang(1-7)、MasR水平降低(P<0.05),ACE、AngⅡ水平升高(P<0.05);模型组与抑制剂+奥司他韦组各指标比较差异无统计学意义(P>0.05);与对照组相比,奥司他韦组、激动剂组、激动剂+奥司他韦组ACE2、Ang(1-7)、MasR水平升高(P<0.05),ACE、AngⅡ水平降低(P<0.05);奥司他韦组与激动剂组各指标比较差异无统计学意义(P>0.05);与奥司他韦组相比,激动剂+奥司他韦组ACE2、Ang(1-7)、MasR水平升高(P<0.05),ACE、AngⅡ水平降低(P<0.05)。结论 奥司他韦通过提高ACE2/Ang(1-7)/Mas受体轴水平及降低炎症因子水平,改善肺炎幼鼠肺功能。
Objective To study the effects of oseltamivir on ACE2/Ang(1-7)/MasR axis,lung injury and inflammation in young mice with pneumonia.Methods Fifty SPF male SD pups were purchased from Guangzhou Genio Biotechnology Co.,LTD.,and 12 of the 50 healthy pups were randomly selected as the healthy group for control.The remaining 38 mice were modeled with influenza virus,and 2 mice died accidentally during the modeling.The 36 successfully modeled mice were divided into model group,oseltamivir group and control group by random number table method,with 12 mice in each group.Young mice in the healthy group and model group were routinely fed,and the young mice in the oseltamivir group were given 10mg/kg oseltamivir orally,once a day,for 5 days.Rats in control group were injected with azithromycin 75mg/mL once a day for 1 w.Results Compared with healthy group,the serum LEVELS of IL-6,IL-8,TNF-αand apoptosis rates in model group,oseltamivir group and control group were increased(P<0.05),and the levels of IL-6,IL-8,TNF-αand apoptosis rates were decreased after oseltamivir intervention(P<0.05).Compared with healthy group,FEF50,FEF75,MMF and PEF levels in model group were decreased(P<0.05),and lung coefficient was increased(P<0.05).After oseltamivir intervention,FEF50,FEF75,MMF and PEF levels were increased(P<0.05),and lung coefficient was decreased(P<0.05).The lung tissue structures of the mice were different.Compared with healthy group,the levels of ACE2,Ang(1-7)and MasR in model group,oseltamivir group,control group,inhibitor group,agonist group,agonist+oseltamivir group and inhibitor+oseltamivir group were decreased(P<0.05),while the levels of ACE and Angⅱwere increased(P<0.05).Compared with model group,the levels of ACE2,Ang(1-7)and MasR in oseltamivir group,control group,agonist group and agonist+oseltamivir group were increased(P<0.05),while the levels of ACE and AngⅡwere decreased(P<0.05).The levels of ACE2,Ang(1-7)and MasR in inhibitor group were decreased(P<0.05).The levels of ACE and AngⅡincreased(P<0.05).There was no significant difference between model group and inhibitor+oseltamivir group(P>0.05).Compared with control group,the levels of ACE2,Ang(1-7)and MasR in oseltamivir group,agonist group and agonist+oseltamivir group were increased(P<0.05),while the levels of ACE and AngⅡwere decreased(P<0.05).There was no significant difference between oseltamivir group and agonist group(P>0.05).Compared with oseltamivir group,the levels of ACE2,Ang(1-7)and MasR in agonist+oseltamivir group were increased(P<0.05),while the levels of ACE and Angⅱwere decreased(P<0.05).Conclusion Oseltamivir improves lung function in young pneumonia mice by increasing ACE2/Ang-(1-7)/Mas receptor axis and decreasing inflammatory factors.
作者
黄蕊
翟英辰
陈煜
林辰曦
陈凌
林兴盛
HUANG Rui;ZHAI Yingchen;CHEN Yu;LIN Chenxi;CHEN Ling;LIN Xingsheng(Zhongshan Hospital Affiliated to Xiamen University,Xiamen 361000,Fujian,China;Qingdao Women's and Children's Hospital,Qingdao 266011,Shandong,China;Fujian Jinshan Hospital,Fuzhou 350028,China)
出处
《西部医学》
2023年第4期495-500,共6页
Medical Journal of West China
基金
福建省卫生健康科研人才培养项目(2019-CX-12)。