基于Keap1/Nrf2/ARE信号通路探讨黄芪甲苷对脂多糖诱导的小鼠急性肺损伤的保护作用  

PROTECTIVE EFFECT OF ASTRAGALOSIDE IV ON LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY IN MICE BASED ON KEAP1/NRF2/ARE SIGNALING PATHWAYS

作　　者：赵红英[1] 谷倩倩 王文娟[1] ZHAO Hongying;GU Qianqian;WANG Wenjuan(Department of Geriatrics,Cangzhou Central Hospital,Cangzhou 061000,China)

机构地区：[1]河北省沧州市中心医院老年医学科,061000

出　　处：《中国煤炭工业医学杂志》2021年第6期566-571,共6页Chinese Journal of Coal Industry Medicine

基　　金：河北省科技计划项目(编号:17277725D)。

摘　　要：目的基于Kelch样环氧氯丙胺相关蛋白1(Keap1)/核转录因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)信号通路探讨黄芪甲苷对脂多糖诱导的小鼠急性肺损伤(ALI)的保护作用。方法将40只BALB/c小鼠随机分为对照组、模型组、阳性对照组及黄芪甲苷组,各10只,采用脂多糖诱导构建小鼠ALI模型(对照组除外),阳性对照组腹腔注射2 mg/kg地塞米松,黄芪甲苷组腹腔注射50 mg/kg黄芪甲苷,连续处理3 d。末次给药2 h后取小鼠肺组织,观察ALI小鼠肺组织病理学改变情况,并检测肺组织中Keap1、Nrf2、血红素氧合酶1(HO-1)mRNA和蛋白表达水平以及超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)、谷胱甘肽酶(GSH-Px)活性及丙二醛(MDA)含量。结果与对照组比较,模型组小鼠肺组织干湿比(W/D)比值、肺含水量比值、肺损伤积分、Keap1表达及MPO活性、MDA含量明显升高,Nrf2、HO-1表达及SOD、GSH-Px活性明显降低(P<0.05)。与模型组比较,黄芪甲苷组、阳性对照组肺组织W/D比值、肺含水量比值、肺损伤积分、Keap1表达及MPO活性、MDA含量明显降低(P<0.05),Nrf2、HO-1表达及SOD、GSHPx活性明显升高(P<0.05)。结论黄芪甲苷对脂多糖诱导的小鼠ALI具有明显保护作用,其机制可能与激活Keap1/Nrf2/ARE信号通路有关。Objective To investigate the protective effect of astragaloside IV on lipopolysaccharide-induced acute lung injury(ALI) in mice based on Kelch-like ECH-associated protein 1(Keap1)/nuclear factor-E2-related factor 2(Nrf2)/antioxidant response element(ARE) signaling pathways.Methods Forty BALB/c mice were randomly divided into control group, model group, positive control group and astragaloside IV group, with ten mice in each group.Lipopolysaccharide was adopted to construct the ALI mice model except for the control group, and the positive control group was intraperitoneally injected with 2 mg/kg dexamethasone and the astragaloside IV group was intraperitoneally injected with 50 mg/kg astragaloside IV,and they were continuously treated for 3 d.The lung tissues in mice were taken at 24 h after the last administration to observe the pathological changes of lung tissue in mice with ALI.The mRNA and protein expression levels of Keap1,Nrf2 and heme oxygenase 1(HO-1) and levels of superoxide dismutase(SOD),myeloperoxidase(MPO),glutathione peroxidase(GSH-Px) and malondialdehyde(MDA) were detected in lung tissues.Results Compared with the control group, the wet-to-dry weight ratio(W/D),lung water content, lung injury score, Keap1 expression, MPO activity and MDA level were significantly increased while the expressions of Nrf2 and HO-1,SOD level and GSH-Px activity were significantly decreased in the model group(P<0.05).The W/D ratio, lung water content, lung injury score, Keap1 expression, MPO activity and MDA level in lung tissues of the astragaloside IV group and the positive control group were significantly reduced(P<0.05) while the expressions of Nrf2 and HO-1 and SOD level and GSH-Px activity were significantly risen(P<0.05) compared with those in the model group.Conclusion Astragaloside IV has a significant protective effect on mice with lipopolysaccharide-induced ALI,and its mechanism may be related to the activation of Keap1/Nrf2/ARE signaling pathways.

关 键 词：黄芪甲苷 脂多糖 急性肺损伤 Kelch样环氧氯丙胺相关蛋白1 核转录因子E2相关因子2 

分 类 号：R563[医药卫生—呼吸系统]