慢性阻塞性肺疾病进程与肺支气管上皮细胞MRP1功能改变的相关性研究简

目的：研究慢性阻塞性肺疾病（COPD）进程与肺支气管上皮细胞多药耐药相关蛋白1（MRP1）功能改变的相关性。方法：采用烟熏复合雾化吸入木瓜蛋白酶法制备COPD模型大鼠，将制备过程中的大鼠随机分成不同进程组，抑制剂组（在造模过程中给予MRPl抑制剂丙磺舒组），另设正常对照组和丙磺舒对照组。以上各组均测定大鼠的肺功能；除抑制剂组外，分别测定大鼠的肺上皮细胞通透性，检查肺上皮细胞完整性；并在静脉注射酚红后，测定支气管肺泡灌洗液（BALF）中酚红浓度和血浆中酚红浓度，以BALF中酚红浓度／血浆中酚红浓度的比值为评价COPD肺支气管上皮细胞MRP1的功能指标。结果：随着造模的进程，COPD大鼠肺功能逐渐降低，造模45d后差异具有统计学意义；BALF中酚红浓度/血浆中酚红浓度的比值逐渐降低，但各组肺上皮细胞通透性功能未发生明显改变；肺上皮细胞完整性良好。与正常对照组比较，在造模过程中，同时给予丙磺舒30d后，肺功能显著性降低；同时与不同进程组60d比较，给予MRP1抑制剂造模60d后，大鼠的FEV0．3％／FVC差异具有统计学意义。结论：COPD的进程与肺支气管上皮MRP1功能的改变具有一定的相关性。肺支气管上皮细胞MRP1的功能随着COPD进程逐渐下调，抑制MRP1的功能会进一步加重COPD的肺功能下降，使病情加重。

Research on relationship between the progression of chronic obstruc- tive pulmonary disease and the change of MRP1 function in lung bronchial epithelium

AIM. To study the relationship between different progressions of chronic ob- structive pulmonary disease （COPD） and the change of MRP1 function in lung bronchial epi- thelium. METHODS： Making stimulation with tobacco and papain to establish COPD rat mod- el. According to the principle of random, the rats were divided into the normal group, differ- ent course of COPD groups, probenecid control group and inhibitor groups. The inhibitor groups were given the MRP1 inhibitor probenecid withthe establishing COPD rat model. The function of lung all the rats were evaluated. The permea- bility and integrity of the lung epithelial cells of all the rats were measured, except the inhibitor group. The phenolsulfonphthalein concentration in bronchoalveolar lavage fluid （BALF） and plasma was determined and the concentration of in BALF/plasma ratio was calculated to evaluate the COPD lung bronchial epithelial MRP1 func- tion. RESULTS： With the development of dis- ease, the lung functions of the rats in differentprogression of COPD were gradually reduced. There was a significant difference in 45 days lat- er. With the process of COPD, the ratio of phe- nolsulfonphthalein concentration in BALF and plasma were gradually reduced, but the lung ep- ithelial cell permeability in each groups had not changed and the integrity of the lung epithelial cells was fine. Compared with the normal groups, lung function of the inhibitor group （30 days） was significantly reduced. There was a significant difference in FEV 0.3%/FVC be- tween the different courses of COPD groups andinhibitor groups in 60 days. CONCLUSION： There is a certain correlation between the process of COPD and changes of MRP1 function in lung bronchial epithelial. With the progres- sion of COPD, the function of MRP1 is gradual- ly reduced in lung bronchial epithelium. Inhibi- ting the function of MRP1 can aggravate the lung function of COPD.