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

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (1): 8-14.

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

汪辰吟¹, 陶秀华^1,2, 张弦^1,3, 汪电雷¹, 陈金佩¹, 杨丽丽¹, 曹银^1,4, 汪珊珊¹

¹安徽中医药大学药学院,合肥 230038,安徽;
²安徽中人科技有限责任公司药理组,合肥 230088,安徽;
³淮南市第一人民医院药剂科,淮南 232007,安徽;
⁴合肥市第四人民医院药剂科,合肥 230022,安徽

收稿日期:2013-03-30 修回日期:2014-01-10 出版日期:2014-01-27 发布日期:2014-02-12
通讯作者: 汪电雷,男,博士,副教授,硕士研究生导师,研究方向:药物代谢动力学。Tel: 0551-65169230 E-mail: dlwang@ahtcm.edu.cn
作者简介:汪辰吟,女,硕士研究生,研究方向:药物代谢动力学。Tel: 0551-65169230 E-mail: 395693237@qq.com
基金资助:
国家自然科学基金(81001592);教育部科学技术重点项目资助(210101);安徽高校省级自然科学研究重点项目资助(KJ2010A210, KJ2012A186)

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

WANG Chen-yin¹, TAO Xiu-hua^1,2, ZHANG Xuan^1,3,WANG Dian-lei¹, CHEN Jin-pei¹, YANG Li-li¹, CAO Yin^1,4, WANG Shan-shan¹

¹College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, Anhui, China;
²Pharmacology Dept,Anhui Sino-Implant Co.,Ltd, Hefei 230088, Anhui, China;
³Pharmacy Dept, the First People's Hospital of Huainan, Huainan 232007, Anhui, China;
⁴Pharmacy Dept,the Fourth People's Hospital of Hefei, Hefei 230022, Anhui, China

Received:2013-03-30 Revised:2014-01-10 Online:2014-01-27 Published:2014-02-12

摘要/Abstract

摘要： 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MRP1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 45 d 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 30 d 后,肺功能显著性降低;同时与不同进程组 60 d 比较,给予MRP1抑制剂造模 60 d 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。

关键词: 慢性阻塞性肺疾病, 进程, 多药耐药相关蛋白1, 功能, 相关性

Abstract: AIM: To study the relationship between different progressions of chronic obstructive pulmonary disease (COPD) and the change of MRP1 function in lung bronchial epithelium.METHODS: Making stimulation with tobacco and papain to establish COPD rat model. According to the principle of random, the rats were divided into the normal group, different course of COPD groups, probenecid control group and inhibitor groups.The inhibitor groups were given the MRP1 inhibitor probenecid with the establishing COPD rat model. The function of lung all the rats were evaluated. The permeability 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 function.RESULTS: With the development of disease, the lung functions of the rats in different progression of COPD were gradually reduced.There was a significant difference in 45 days later. With the process of COPD, the ratio of phenolsulfonphthalein concentration in BALF and plasma were gradually reduced, but the lung epithelial 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 FEV0.3%/FVC between the different courses of COPD groups and inhibitor 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 progression of COPD, the function of MRP1 is gradually reduced in lung bronchial epithelium. Inhibiting the function of MRP1 can aggravate the lung function of COPD.

Key words: COPD, Progression, MRP1, Function, Correlation

中图分类号:

R965.2

汪辰吟, 陶秀华, 张弦, 汪电雷, 陈金佩, 杨丽丽, 曹银, 汪珊珊. 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[J]. 中国临床药理学与治疗学, 2014, 19(1): 8-14.

WANG Chen-yin, TAO Xiu-hua, ZHANG Xuan,WANG Dian-lei, CHEN Jin-pei, YANG Li-li, CAO Yin, WANG Shan-shan. Research on relationship between the progression of chronic obstructive pulmonary disease and the change of MRP1 function in lung bronchial epithelium[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(1): 8-14.

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