盐酸班布特罗对慢性阻塞性肺疾病大鼠的作用机制研究  

Effet and mechanism of bambuterol hydrochloride in rats with chronic obstructive pulmonary disease

作　　者：张志大[1] 黄健[1] 李希玖 李飞妹 ZHANG Zhi-da;HUANG Jian;LI Xi-jiu;LI Fei-mei(Department of Respiratory and Critical Care,Jiangxi Chest Hospital,Nanchang 330006,Jiangxi Province,China;Department of Pathology,Jiangxi Chest Hospital,Nanchang 330006,Jiangxi Province,China)

机构地区：[1]江西省胸科医院呼吸与危重症科,江西南昌330006 [2]江西省胸科医院病理科,江西南昌330006

出　　处：《中国临床药理学杂志》2022年第1期23-26,共4页The Chinese Journal of Clinical Pharmacology

基　　金：江西省卫生计生委科技计划基金资助项目(20185470)。

摘　　要：目的研究盐酸班布特罗对慢性阻塞性肺疾病(COPD)大鼠的作用机制。方法用烟熏法建立COPD大鼠模型。按照体重将大鼠随机分为4组:正常组(10只)、模型组(15只)、班布特罗组(15只)、激动剂组(15只)。造模后,班布特罗组灌胃盐酸班布特罗2 mg·kg^(-1),激动剂组在班布特罗组基础上腹腔注射脂多糖0.5 mg·kg^(-1),正常组和模型组给予同体积生理盐水,1次/天,连续45 d。苏木精-伊红染色测量气道重构指标;用酶联免疫吸附法检测白细胞介素-8(IL-8)含量;用免疫印迹法检测肺组织Toll样受体4(TLR4)蛋白表达量、磷酸化核转录因子κB p65(p-NF-κB p65)/NF-κB p65蛋白表达(灰度值)。结果正常组、模型组、班布特罗组和激动剂组的管壁厚度/外径分别为(6.27±0.83)%,(13.89±1.26)%,(8.17±1.10)%和(11.29±1.25)%;这4组的IL-8水平分别为(95.56±10.28),(212.67±29.67),(145.87±23.63)和(180.66±20.54)pg·mg^(-1);这4组的TLR4蛋白表达量分别为0.15±0.03,0.70±0.08,0.36±0.04和0.53±0.06;这4组的p-NF-κB p65/NF-κB p65分别为0.18±0.03,0.77±0.08,0.35±0.05和0.61±0.07。模型组与正常组比较,或班布特罗组与模型组比较,或激动剂组与班布特罗组比较,上述指标的差异均有统计学意义(均P<0.05)。结论盐酸班布特罗可减少COPD大鼠炎症介质的释放,抑制气道重构,这可能通过抑制TLR4/NF-κB信号通路来实现。Objective To study the effect and mechanism of bambutero hydrochloride on chronic obstructive pulmonary disease (COPD) rats.Methods The rats were established a COPD model by smoking method.The rats were randomly divided into four groups according to their body weight:normal group (n=10),model group (n=15),bambutero group (n=15),and agonist group (n=15).After modeling the bambuterol group was gavage with bambuterol hydrochloride 2mg·kg^(-1),the agonist was gavage with bambuterol hydrochloride 2mg·kg^(-1),intraperitoneal injection of lipopolysaccharide (LPS) 0.5mg·kg^(-1).The normal group and the model group were given the same volume of normal saline,once a day,for consecutive 45 d.The airway remodeling indexes were detected by HE staining.The interleukin-8(IL-8) content were detected by enzyme-linked immunosorbent assay.The expression (gray value) of Toll-like receptor 4 (TLR4) protein and phosphorylated nuclear transcription factorκB p65 (p-NF-κB p65)/NF-κB p65were detected by Western blotting.Results The wall thickness/outer diameter of the normal group,model group,bambuterol group,agonist group were (6.27±0.83)%,(13.89±1.26)%,(8.17±1.10)%,(11.29±1.25)%.The IL-8 levels of the 4 groups were (95.56±10.28),(212.67±29.67),(145.87±23.63) and(180.66±20.54) pg·mg^(-1).The TLR4 protein expression levels of the 4 groups were0.15±0.03,0.70±0.08,0.36±0.04 and 0.53±0.06.The ratio of p-NF-κB p65/NF-κB p65 of the 4 groups were 0.18±0.03,0.77±0.08,0.35±0.05 and 0.61±0.07.Comparison between the model group and the normal group,or between the bambuterol group and the model,or the agonist group and bambuterol group,the differences of the factors were significant (all P<0.05).Conclusion Bambuterol hydrochloride can reduce the release of inflammatory mediators in COPD rats,inhibit airway remodeling,and reduce lung pathological changes,which may be achieved by inhibiting the TLR4/NF-κB signaling pathway.

关 键 词：慢性阻塞性肺疾病 盐酸班布特罗 气道重构 炎症介质 基质金属蛋白酶-9 

分 类 号：R97[医药卫生—药品]