依达拉奉减轻慢性阻塞性肺疾病大鼠氧化应激和炎性反应  

Edaravone reduces oxidative stress and inflammation in COPD rats

作　　者：程涛[1] 马程远 尹亚楠[1] 孙贝贝[2] CHENG Tao;MA Cheng-yuan;YIN Ya-nan;SUN Bei-bei(Department of Respiratory and Critical Care Medicine, the First People's Hospital of Nanyang, Nanyang 473000;Department of Respiratory Medicine, Henan Provincial People's Hospital, Zhengzhou 450000, China)

机构地区：[1]南阳市第一人民医院呼吸与危重症医学科,河南南阳473000 [2]河南省人民医院呼吸内科,河南郑州450000

出　　处：《基础医学与临床》2021年第10期1457-1462,共6页Basic and Clinical Medicine

基　　金：河南省科技研发专项(152102310147)。

摘　　要：目的探究依达拉奉(EDA)对慢性阻塞性肺疾病(COPD)大鼠氧化应激和炎性反应的作用机制。方法将大鼠随机分为对照组、模型组、EDA高、中和低剂量组,每组10只。气管滴注脂多糖(LPS)联合烟熏制备COPD模型,腹腔注射40、20、10 mg/kg EDA。造模28 d后,检测肺功能和肺组织湿干重比(W/D);ELISA法检测肺组织SOD、MDA、TNF-α、IL-1β、IL-6水平;HE染色观察肺组织病理学形态;Western blot检测caspase-3、MMP-9、TLR4、MyD88、NF-κB p65蛋白表达和IκBα磷酸化。结果与对照组比较,模型组静息呼吸频率、气道阻力(RI)升高,吸气峰流速(PIF)和动态肺顺应性(Cdyn)值降低,肺损伤明显,肺组织SOD活力降低,MDA、TNF-α、IL-1β、IL-6含量增加,caspase-3、MMP-9、TLR4、MyD88表达及IκBα磷酸化水平升高,NF-κB p65核内转移明显(P<0.05)。与模型组比较,EDA降低静息呼吸频率和RI,升高PIF和Cdyn,减轻肺损伤,增加肺组织SOD活力,减少MDA、TNF-α、IL-1β、IL-6含量,降低caspase-3、MMP-9、TLR4、MyD88表达及IκBα磷酸化水平,NF-κB p65核内转移受限(P<0.05)。结论EDA可改善COPD大鼠肺功能,减轻肺组织损伤及炎性反应和氧化应激水平。Objective To explore the mechanism of edaravone(EDA)on oxidative stress and inflammation in chronic obstructive pulmonary disease(COPD)rats.Methods The rats were randomly divided into control group,model group,EDA high dose group,EDA medium dose group and EDA low dose group,with 10 rats in each group.The COPD model was developed by intratracheal infusion of lipopolysaccharide(LPS)combined with smoking,and rats were injected intra-peritoneally with 40,20,and 10 mg/kg EDA.Twenty-eight days after modeling,the pulmonary function and the wet-to-dry weight ratio(W/D)of the lung tissues were examined.ELISA method was used to detect the level of SOD,MDA,TNF-α,IL-1βand IL-6 in lung tissues.The pathological changes of lung tissues were microscopied with HE staining.Western blot was used to detect the protein expression of Caspase-3,MMP-9,TLR4,MyD88,NF-κB p65 protein expression and IκBαphosphorylation.Results Compared with control group,the resting breathing frequency and airway resistance(RI)of model group increased,the values ofpeak inhale flow(PIF)and dynamic lung compliance(Cdyn)decreased;the lung injury was obvious,the SOD activity of the lung tissues decreased,the contents of MDA,TNF-α,IL-1β,and IL-6 increased,and Caspase-3.MMP-9,TLR4,MyD88 expression and IκBαphosphorylation increased,and NF-κB p65 intranuclear metastasis was obvious(P<0.05).Compared with model group,EDA reduced resting respiratory frequency,RI,increased PIF and Cdyn,reduced lung injury,increased SOD activity of lung tissues,reduced MDA,TNF-α,IL-1β,IL-6 contents,and reduced caspase-3,MMP-9,TLR4,MyD88 expression and IκBαphosphorylation,NF-κB p65 nuclear metastasis was restricted(P<0.05).Conclusions EDA can improve the lung function of COPD rats,reduce lung tissues damage,inflammation and oxidative stress.

关 键 词：慢性阻塞性肺疾病 依达拉奉 氧化应激 炎性反应 

分 类 号：R965[医药卫生—药理学]