TLR4在慢性支气管炎大鼠气道粘液高分泌中的作用  

TLR4 Mediates Endotoxin-induced Chronic Bronchitis and Airway Mucus Hypersecretion in Rats

作　　者：万宁[1] 张建勇[2] 唐凤鸣[1] 李永春[1] 张健[1] 陈德[1] 

机构地区：[1]宜宾市第一人民医院呼吸内科,四川宜宾644000 [2]遵义医学院附属医院呼吸二科,贵州遵义563000

出　　处：《四川医学》2015年第11期1521-1524,共4页Sichuan Medical Journal

基　　金：贵州省科学技术基金项目(编号:黔科合J字[2007]2218号)

摘　　要：目的观察TLR4在细菌内毒素(LPS)致慢性支气管炎大鼠气道粘液高分泌中的作用。方法 SPF级雄性Wistar大鼠40只,随机分为4组,正常对照组(NS组)10只,慢性支气管炎组(LPS组)10只,多粘菌素B干预组(LPS+PMB组)10只,多粘菌素B自身对照组(PMB组)10只。用气管内注入LPS 200μg/200μL及每日LPS溶液雾化吸入1h的方法建立慢性支气管炎动物模型,3周后对大鼠肺脏进行病理学检查,肺组织阿先蓝-过碘酸雪夫(AB-PAS)阳染面积,用免疫组化法观察粘蛋白Muc5AC、TLR4在支气管肺内的表达及荧光定量RT-PCR Muc5AC mRNA、TLR4 mRNA在肺内的表达。结果 LPS组在AB-PAS阳染面积、粘蛋白Muc5AC、TLR4蛋白及Muc5AC mRNA、TLR4 mRNA表达与LPS+PMB组比较差异有统计学意义(P<0.05),NS组和PMB组在上述指标则组间差异无统计学意义(P>0.05)。结论 TLR4介导LPS诱发的慢性呼吸道炎症反应可能导致气道粘蛋白基因Muc5AC mRNA的高表达和粘蛋白Muc5AC的高分泌。多粘菌素B可能通过抑制肺组织TLR4 mRNA及其蛋白的表达而抑制气道粘液高分泌。Objective To investigate role of Toll-like receptor 4（ TLR4） in endotoxin-induced airway mucus hypersecretion in chronic bronchitis rats. Methods Forty rats were randomly divided into four groups： control group（ NS group,n = 10）,chronic bronchitis model group（ LPS group,n = 10）,polymyxin B（ PMB） treatment group（ LPS ＋ PMB group,n = 10）,PMB control group（ PMB group,n = 10）. The rat model of chronic bronchitis was established by intratracheal instillation 200μg /200μl of lipopolysaccharide（ LPS） and daily exposure to LPS smog. After three weeks,the pathomorphological Changes in the lung were analyzed,the goblet cell of airway wall was observed by alcian blue / periodic acid schiff（ AB-PAS） staining,the expressions of Mucin5AC（ Muc5AC） and TLR4 in lung tissue were observed by immuneohistochemical staining,the expressions of Muc5 AC mRNA and TLR4 mRNA in lung tissue were observed by real time fluorescence quantitative reverse transcription polymerase（ RT-PCR）. Results The goblet cell of airway wall,the expression of Mucus secretion and Muc5 AC mRNA in airway,the expression of TLR4 mRNA and TLR4 positive staining of lung tissue obviously decreased in PMB treatment group which compared with chronic bronchitis model group（ P 〈0. 05）. Conclusion The current studys suggests that polymyxin B may inhibit endotoxin-induce airway mucus hypersecretion in rats,which were mediated by TLR4.

关 键 词：慢性支气管炎 内毒素 多粘菌素B TLR4 MUC5AC 

分 类 号：R562.21[医药卫生—呼吸系统]