五倍子酯提物抗流感病毒诱导的小鼠急性肺损伤作用机制  

Mechanism of Action of Galla chinensis Ethyl Acetate Extract in Alleviating Acute Lung Injury Induced by Influenza Virus in Mice

作　　者：张彧[1] 吴东升[1] 齐堃 曾丽红[1] 张银银[1] 李玲[1] 邓奕辉[1] ZHANG Yu;WU Dongsheng;QI Kun;ZENG Lihong;ZHANG Yinyin;LI Ling;DENG Yihui(Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《湖南中医药大学学报》2018年第12期1366-1370,共5页Journal of Hunan University of Chinese Medicine

基　　金：湖南省自然科学基金项目(2016JJ2095);湖南省大学生创新创业训练计划项目(2016-293)

摘　　要：目的探索Toll样受体4(TLR4)在A型流感病毒所致小鼠急性肺损伤中的作用,进一步探讨五倍子酯提物的干预机制。方法实验设正常组、模型组、五倍子酯提物组和奥司他韦组,以流感病毒小鼠肺适应株A/PR/8/34滴鼻感染C57BL小鼠,建立小鼠急性肺损伤模型。病毒感染后第1天开始予以相应干预,共6 d。分别于第2、4、6天处理动物。观察肺组织大体解剖学变化,肺组织切片病理学变化,ELISA法检测肺泡灌洗液中白细胞介素-6(IL-6)、白细胞介素-10(IL-10)水平,Western blot法检测肺组织中TLR4、MyD88、TRAF6的蛋白表达。结果流感病毒感染小鼠后,模型组小鼠肺脏充血、水肿,外观呈暗褐色,肺泡间质水肿、肺泡腔变小,内有大量炎细胞浸润,肺泡灌洗液中IL-6、IL-10水平及肺组织中TLR4、MyD88、TRAF6蛋白表达升高,与正常组相比,差异有显著统计学意义(P<0.01)。与模型组相比,五倍子酯提物组能减轻肺部病变,降低肺泡灌洗液中IL-6、IL-10水平及肺组织中TLR4、MyD88、TRAF6蛋白表达水平,差异有显著统计学意义(P<0.01)。结论五倍子酯提物可通过抑制TLR4的活化及下游MyD88依赖的转导路径,减少炎性因子的转录生成,减轻肺部炎症,减缓急性肺损伤进程。Objective To explore the role of Toll-like receptor4(TLR4)in acute lung injury induced by influenza A virus in mice,and to further explore the mechanism of action of Galla chinensis ethyl acetate extract.Methods The mice were divided into normal group,model group,Galla chinensis extracts group,and oseltamivir group.A mouse model of acute lung injury was established by infecting C57BL mice through nasal dripping with mouse lung-adapted influenza virus strain A/PR/8/34.Corresponding treatments were administered from the first day after virus infection,and repeated for6days.The animals were disposed of on days2,4,and6.The gross changes of the lungs and the pathological changes of lung tissue sections were assessed;ELISA was used to determine the levels of interleukin-6(IL-6)and interleukin-10(IL-10)in alveolar lavage fluid;Western blot was used to determine the protein expression of TLR4,MyD88,and TRAF6in lung tissues.Results After influenza virus infection,compared with the normal group,the model group showed hyperemia and edema of the lung with dark-brown appearance,alveolar interstitial edema,and decreased size of alveolar cavities with extensive inflammatory cell infiltration,as well as significantly increased levels of IL-6and IL-10in alveolar lavage fluid and protein expression of TLR4,MyD88,and TRAF6in lung tissues(P<0.01).Compared with the model group,the Galla chinensis extract group had alleviated lung lesions,as well as significantly reduced levels of IL-6and IL-10in alveolar lavage fluid and protein expression of TLR4,MyD88,and TRAF6in lung tissues(P<0.01).Conclusion Galla chinensis extract can reduce the transcription of inflammatory factors,alleviate lung inflammation,and slow down the progression of acute lung injury by inhibiting the activation of TLR4and downstream MyD88-dependent transduction pathway.

关 键 词：五倍子酯提物 流感病毒 TOLL样受体4 急性肺损伤 白细胞介素-6 白细胞介素-10 

分 类 号：R285.5[医药卫生—中药学] R563[医药卫生—中医学]