基于TLR4/NF-κB信号通路探讨盐酸班布特罗干预COPD模型大鼠血管重塑的机制研究  

Mechanism of bambuterol hydrochloride intervening the vascular remodeling in rats model with COPD based on TLR4/NF-κB signal pathway

作　　者：郑春晨[1] 佘晖[1] ZHENG Chun-chen;SHE Hui(Fuzhou Second Hospital,Fuzhou 350007,China)

机构地区：[1]福州市第二医院,350007

出　　处：《中国现代药物应用》2022年第15期191-194,共4页Chinese Journal of Modern Drug Application

基　　金：福州市科技局社会发展项目(项目编号:2020-WS-93)。

摘　　要：目的观察Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路,研究盐酸班布特罗干预慢性阻塞性肺疾病(COPD)模型大鼠血管重塑的作用。方法30只SPF级雄性SD大鼠,随机分为空白对照组、模型组、给药组,各10只。模型组、给药组给予大鼠气管灌注脂多糖(LPS)与烟熏建立COPD模型;空白对照组大鼠不烟熏,气道内滴注等体积生理盐水代替。造模成功后,给药组大鼠给予盐酸班布特罗灌胃;空白对照组和模型组大鼠给予同体积生理盐水灌胃。第45天后取大鼠肺组织行免疫组化测定TLR4、NF-κB蛋白水平,酶联免疫吸附试验法(ELISA)测定大鼠血管重塑指标血管内皮生长因子(VEGF)、内皮素-1(ET-1)、结缔组织生长因子(CTGF)的表达水平。观察三组大鼠COPD模型建立后肺组织HE染色情况;比较三组大鼠肺血管TLR4、NF-κB表达水平及血清VEGF、ET-1、CTGF表达水平。结果空白对照组大鼠肺血管TLR4、NF-κB表达水平分别为(1.829±1.392)、(13.667±5.530),模型组分别为(10.585±3.347)、(79.380±54.940),给药组分别为(8.352±2.568)、(44.040±12.850),模型组和给药组大鼠肺血管TLR4、NF-κB表达水平均高于空白对照组,模型组高于给药组,三组比较差异具有统计学意义(P<0.05)。空白对照组大鼠血清ET-1、CTGF、VEGF表达水平分别为(0.167±0.094)、(174.64±109.48)、(12.058±6.640),模型组分别为(1.430±0.930)、(801.81±219.60)、(119.660±88.750),给药组分别为(0.717±0.405)、(340.88±138.79)、(60.320±20.200),模型组和给药组大鼠血清VEGF、ET-1、CTGF表达水平均高于空白对照组,模型组高于给药组,三组比较差异具有统计学意义(P<0.05)。结论盐酸班布特罗可能通过抑制受体TLR4表达,降低配体LPS和烟雾对TLR4/NF-κB信号通路的诱导作用,下调血管平滑肌增生相关因子VEGF、ET-1、CTGF的合成与分泌,从而延缓或阻滞COPD血管重塑的过程。Objective To investigate toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signal pathway and study the effect of bambuterol hydrochloride intervening the vascular remodeling in rats model with chronic obstructive pulmonary disease(COPD).Methods 30 SPF-grade male SD rats were randomly divided into a blank control group,a model group and an administration group,with 10 rats in each group.Rats of the model group and the administration group were provided with intratracheal instillation of lipopolysaccharide(LPS)and smoking so as to establish a COPD model;while rats of the blank control group received intratracheal instillation of an equal volume of normal saline instead of smoking.After modeling,the rats of the administration group received a stomach irrigation of bambuterol hydrochloride.After 45 days,lung tissues of the rats were taken to determine the level of TLR4 and NF-κB proteins with immunohistochemistry and measure the expression levels of vascular endothelial growth factor(VEGF),endothelin-1(ET-1)and connective tissue growth factor(CTGF)by enzymelinked immunosorbent assay(ELISA).HE staining of lung tissue was observed after rats model with COPD were established in three groups.Expression levels of TLR4,NF-κB and serum VEGF,ET-1,CTGF in pulmonary vessels of the rats of the three groups.Results The expression levels of TLR4 and NF-κB in pulmonary vascular of rats were(1.829±1.392)and(13.667±5.530)in the blank control group,(10.585±3.347)and(79.380±54.940)in the model group,and(8.352±2.568)and(44.040±12.850)in the administration group.The expression levels of TLR4 and NF-κB in pulmonary vessels of the rats of the model group and the administration group were higher than that of the blank control group,and the expression level of the model group was higher than that of the administration group;and the differences were statistically significant(P<0.05).Expression levels of serum ET-1,CTGF,VEGF in pulmonary vessels of the rats were(0.167±0.094),(174.64±109.48),(1.430±0.930)in the blank control g

关 键 词：慢性阻塞性肺疾病 盐酸班布特罗 血管重塑 动物模型 

分 类 号：R965[医药卫生—药理学]