选择性磷酸二酯酶4抑制剂对气道黏液高分泌模型大鼠肺组织水通道蛋白质5表达的影响  

Effects of selective phosphodiesterase 4 inhibitor on expression of aquaporin 5 in airway mucus hypersecretion model of rats

作　　者：贾卫华[1] 杨鹏[1] 李静[1] 田增莲[1] 

机构地区：[1]山西医科大学附属太原钢铁集团有限公司总医院呼吸科,太原030003

出　　处：《中华医学杂志》2013年第8期619-622,共4页National Medical Journal of China

摘　　要：目的探讨选择性磷酸二酯酶4（PDFA）抑制剂对气道黏液高分泌模型大鼠肺组织中水通道蛋白质5（AQP5）表达的影响。方法40只清洁级健康雄性sD大鼠完全随机化法随机分为4组，每组10只：正常对照组（给予生理盐水雾化吸人12d）、药物对照组（给予YM976灌胃12d）、模型组（给予丙烯醛雾化吸人12d）、药物干预组（给予丙烯醛雾化吸人同时给予YM976灌胃12d），大鼠右肺中叶固定包埋，行HE染色观察肺组织小气道组织学变化，阿辛蓝染色观察杯状细胞黏蛋白分泌情况，AQP5免疫组化染色观察选择性PDFA抑制剂对AQP5表达的影响。大鼠右肺下叶提取肺组织总RNA和蛋白，以反转录-PCR检测AQP5的mRNA表达水平的变化，以Western印迹法检测AQP5蛋白质水平的变化。结果与模型组相比，药物干预组中的气道黏液腺增生和黏液过度分泌明显减轻，阿辛蓝相对阳染面积明显减少（10．23％±0．94％比14．74％±1．06％，P〈0．05）。同时，药物干预组的肺组织AQP5的mRNA和蛋白相对表达量分别为1．26±0．19和0．56±0．13，均明显高于模型组的0．96±0.17和0．43±0．15（均P〈0．05）。结论PDFA抑制剂可减轻气道黏液高分泌大鼠肺组织的病理损伤，增强AQP5的表达。Objective To explore the mechanism of selective phosphodiesterase 4 （PDFA） inhibitor and observe its effects on the in vitro expression of aquaporin 5 （ AQP5 ） in a rat model of airway mucus hypersecretion. Methods Forty healthy male rats were randomized into 4 groups （n = 10 each ）. The normal control and drug control groups underwent normal saline aerosol inhalation or YM976 lavage respectively for 12 days while the model and treatment groups aerolein atomization inhalation or crolein atomization inhalation plus YM976 lavage respectively for 12 days. The middle lobe of right lung were fixed, embedded and stained by hematoxylin and eosin to observe the histological changes of small airway. The mucin secretion by goblet cells in lung tissue was tested by aleian blue staining. And the effects of selective PDFA inhibitor on the expression of AQP5 were detected by immunohistochemical stain. Reverse transcription-polymerase chain reaction and Western blot were used to determine the levels of AQP5 mRNA and protein. Results In the treatment group, mucus gland hyperplasia and airway mucus hypersecretion and positive staining area ratio of alcian blue staining decreased significantly compared with the model group （ 10. 23% ±0. 94% vs 14. 74% ± 1.06% , P 〈0. 05）. And the expression of AQP5 mRNA （ 1.26 ±0. 19） and protein （0. 56± 0. 13 ） also declined significantly versus the model group （（ 0. 96 ± 0. 17 ）, （0. 43 ± 0. 15 ）, P 〈 0. 05）. Condusion Selective PDE4 inhibitors alleviate the pathological damage of lung tissue and enhance the expression of AQP-5 in airway mucus hypersecretion.

关 键 词：磷酸二酯酶抑制剂 水通道蛋白质5 气道黏液高分泌 

分 类 号：R285.5[医药卫生—中药学]