CAJ | 학술논문

目的探讨选择性磷酸二酯酶4(PDE4)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(AQPS)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入12 d)、药物对照组(给予YM976灌胃12 d)、模型组(给予丙烯醛雾化吸入12 d)、药物干预组(给予丙烯醛雾化吸入同时给予YM976灌胃12 d),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PDE4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 PDE4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.
목적 탐토선택성린산이지매4(PDE4)억제제대기도점액고분비모형대서폐조직중수통도단백질5(AQPS)표체적영향.방법 40지청길급건강웅성SD대서완전수궤화법수궤분위4조,매조10지:정상대조조(급여생리염수무화흡입12 d)、약물대조조(급여YM976관위12 d)、모형조(급여병희철무화흡입12 d)、약물간예조(급여병희철무화흡입동시급여YM976관위12 d),대서우폐중협고정포매,행HE염색관찰폐조직소기도조직학변화,아신람염색관찰배상세포점단백분비정황,AQP5면역조화염색관찰선택성PDE4억제제대AQP5표체적영향.대서우폐하협제취폐조직총RNA화단백,이반전록-PCR검측AQP5적mRNA표체수평적변화,이Western인적법검측AQP5단백질수평적변화.결과 여모형조상비,약물간예조중적기도점액선증생화점액과도분비명현감경,아신람상대양염면적명현감소(10.23％±0.94％비14.74％±1.06％,P＜0.05).동시,약물간예조적폐조직AQP5적mRNA화단백상대표체량분별위1.26±0.19화0.56±0.13,균명현고우모형조적0.96±0.17화0.43 ±0.15(균P＜0.05).결론 PDE4억제제가감경기도점액고분비대서폐조직적병리손상,증강AQP5적표체.
Objective To explore the mechanism of selective phosphodiesterase 4 (PDF4)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 acrolein 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 alcian blue staining.And the effects of selective PDF4 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).Conclusion Selective PDE4 inhibitors alleviate the pathological damage of lung tissue and enhance the expression of AQP-5 in airway mucus hypersecretion.