脂多糖诱导的慢性阻塞性肺病模型大鼠肺支气管上皮MRP1功能分析

MRP1 expression and bronchial epithelial function in lipopolysaccharideinduced rat model of chronic obstructive pulmonary disease

目的分析脂多糖(LPS)造模方法对慢性阻塞性肺疾病(COPD)模型大鼠的肺支气管上皮细胞多药耐药相关蛋白1(MRP1)功能的影响。方法利用LPS造模方法制备COPD模型大鼠,设置正常对照组、造模14d组和造模28 d组,分别测定其呼吸功能;以酚红外排水平评价大鼠肺支气管上皮MRP1的功能;同时采用免疫组化法分析各组大鼠肺支气管上皮MRP1的表达。结果与正常对照组比较,LPS处理组造模进程中随时间的延长大鼠的各项肺功能指标明显下降;静脉给予酚红后其BALF中酚红浓度与血浆酚红浓度的比值降低;其肺支气管上皮MRP1蛋白表达显著性降低。结论 LPS造模方法制备COPD模型大鼠,随着造模的进程,其肺支气管上皮细胞MRP1蛋白的功能随之下调。

Objective To study the impact of establishment of lipopolysaccharide （ LPS ）-induced rat model of chronic obstructive pulmonary disease （COPD）on the function of multidrug resistance-associated protein 1（MRP1）in the rat bronchial epithelium .Methods Using intratracheal instillation of LPS to establish COPD rat model .8-week old healthy male Wistar rats were divided into 3 groups （10 rats in each group ）：（1） Normal control;（2） Modeling for 14 days after LPS instillation;（3） Modeling for 28 days after LPS instillation.Pulmonary function and the concentration of phenol red in bronchoalveolar lavage fluid （ BALF） and plasma were measured .The ratio of phenol red concentration in BALF/plasma was used as an index of the MRP 1 function in the rat bronchial epithelium and the expression of MRP 1 in the bronchial epi-thelium was also observed by immunohistochemistry .Results Compared with the normal group , the pulmonary functions of the rats in the model groups were significantly reduced along with the modeling progress .After intravenous administration of phenol red, the ratio of phenol red concentration in BALF/plasma was gradually reduced , and the expression of MRP1 in the bronchial epithelium was significantly decreased .Conclusions COPD rat model can be established by intratracheal LPS instillation, and the function of MRP1 in bronchial epithelium was gradually reduced along with the modeling progress .