氨茶碱对脂多糖诱导的慢性阻塞性肺疾病大鼠肺功能的作用  

Effect of aminophylline on lung function in rats with chronic obstructive pulmonary disease induced by lipopolysaccharide

作　　者：刘芳[1] 杜文秀[1] 张欣[1] 杜俊凤[1] 张颖 迟玉敏[1] LIU Fang;DU Wenxiu;ZHANG Xin;DU Junfeng;ZHANG Ying;CHI Yumin(Department of Respiratory Medicine,Cangzhou Central Hospital,Cangzhou 061000,China)

机构地区：[1]沧州市中心医院呼吸科,沧州061000

出　　处：《西北药学杂志》2022年第6期65-70,共6页Northwest Pharmaceutical Journal

基　　金：河北省2020年度医学科学研究课题计划(编号:20200338)。

摘　　要：目的探讨氨茶碱对脂多糖诱导的慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠肺功能的作用。方法48只大鼠随机取10只作为A组,另38只成功建立COPD模型的36只大鼠以随机体质量排序法分为B组、C组和D组,各12只。C组、D组分别以80、160 mg·kg^(-1)氨茶碱溶液灌胃,A组、B组以等体积生理盐水灌胃。检测各组大鼠第0.3 s用力呼气容积(forced expiratory volume in first 0.3 second,FEV_(0.3))、用力肺活量(forced vital capacity,FVC)、动态肺顺应性及超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、谷胱甘肽(glutataione,GSH)、白细胞介素-8(interleukin-8,IL-8)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;检测Kelch样环氧氯丙烷相关蛋白-1(Kelch-like epichlo-rohydrin-associated protein 1,Keap1)、核因子E2相关因子2(nuclear factor erythroid-2 related factor 2,Nrf2)、血红素氧合酶1(heme oxygenase-1,HO-1)mRNA和蛋白相对表达量。结果与A组比较,3个组FEV_(0.3)、FEV_(0.3)/FVC降低,B组<C组<D组(P<0.05);A组、B组、C组和D组肺顺应性分别为(1.62±0.32)、(0.58±0.13)、(0.96±0.25)、(1.25±0.28)mL·cm H_(2)O^(-1),B组<C组<D组(P<0.05);与A组比较,3个组SOD降低,MDA、GSH、IL-8和TNF-α升高,SOD,B组<C组<D组,MDA、GSH,D组<C组<B组(P<0.05);与B组比较,C、D组泡壁增厚、细支气管渗出和炎性细胞浸润等异常病理变化减轻,其中D组改善更显著;与A组比较,3组Keap1 mRNA及蛋白相对表达量升高,Nrf2、HO-1 mRNA及蛋白相对表达量降低,Keap1 mRNA及蛋白相对表达量,D组<C组<B组,Nrf2、HO-1 mRNA及蛋白相对表达量,B组<C组<D组(P<0.05)。结论氨茶碱可改善脂多糖诱导的COPD大鼠肺功能,调节氧化-抗氧化失衡,作用机制可能与激活Keap1-Nrf2/HO-1信号通路有关。Objective To investigate the effect of aminophylline on lung function in rats with chronic obstructive pulmonary disease(COPD)induced by lipopolysaccharide.Methods Ten of 48 clean grade SD rats were randomly selected as group A.Among the 38 rats,36 rats successfully established COPD model were divided into Group B,Group C and Group D by body mass ranking method,with 12 rats in each group.Group C and group D were given 80 and 160 mg·kg^(-1) aminophylline solution by gavage,while group A and group B were given equal volume of normal saline by gavage.The forced expiratory volume in first 0.3 second(FEV_(0.3)),forced vital capacity(FVC),dynamic lung compliance and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione(GSH),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)were detected.The mRNA and protein expressions of Kelch-like epichlo-rohydrin-associated protein 1(Keap1),nuclear factor erythroid-2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected.Results Compared with group A,the FEV_(0.3) and FEV_(0.3)/FVC in the 3 groups were decreased,group B<group C<group D(P<0.05).The lung compliance in group A,B,C and D were(1.62±0.32),(0.58±0.13),(0.96±0.25)and(1.25±0.28)mL·cmH 2O-1,group B<group C<group D(P<0.05).Compared with group A,the SOD decreased,group B<group C<group D,but MDA,GSH,IL-8 and TNF-αincreased,group D<group C<group B(P<0.05).Compared with group B,the abnormal pathological changes such as the wall thickening,bronchiolar exudation and inflammatory cell infiltration were alleviated in group C and D,especially in Group D.Compared with group A,the relative expressions of Keap1 mRNA and protein in group B,C and D were increased,group D<group C<group B,while the relative expressions of Nrf2 and HO-1 mRNA and protein were decreased,group B<group C<group D(P<0.05).Conclusion Aminophylline can improve the lung function in COPD rats induced by lipopolysaccharide and regulate the imbalance between oxidation and antioxidation.The mechanism may be related to the activation of

关 键 词：氨茶碱 慢性阻塞性肺疾病(COPD) 肺功能 

分 类 号：R965[医药卫生—药理学]