磷酸二酯酶4抑制剂对大鼠肺粘液分泌的影响  

Phosphodiesterase-4 inhibitor YM976 attenuates pulmonary mucus hypersecretion of rats

作　　者：王洵[1] 李继琼[1] 陈磊[1] 王海霞[1] 孙贝贝[1] 汪涛[1] 徐丹[1] 文富强[1] 

机构地区：[1]四川大学华西医院呼吸内科四川大学人类疾病生物治疗国家重点实验室呼吸病学研究室,四川成都610041

出　　处：《西部医学》2008年第3期468-470,共3页Medical Journal of West China

基　　金：国家自然科学基金(No.30370627);国家杰出青年科学基金(No.30425007);美国纽约CMB基金(No.002722)

摘　　要：目的探讨磷酸二酯酶4(PDE4)抑制剂YM976对慢性阻塞性肺疾病(COPD)大鼠肺粘液分泌的影响。方法将40只SD大鼠随机等分为4组:正常对照组、药物对照组、COPD模型组、药物干预组。测定支气管肺泡灌洗液(BALF)中的细胞总数和巨噬细胞绝对计数及百分比,阿辛蓝和MUC5AC免疫组化染色检测MUC5AC表达,RT-PCR检测MUC5AC mRNA在肺组织中的表达。结果YM976可以降低丙烯醛诱导的COPD大鼠BALF中的细胞总数和肺泡巨噬细胞计数及百分比,降低其肺组织MUC5AC的mRNA水平和MUC5AC蛋白表达。结论YM976能有效减少大鼠BALF中细胞总数和巨噬细胞数,从蛋白和基因水平抑制大鼠肺组织MUC5AC的表达。Objective To examine the influence of phosphodiesterase-4 （PDE4） inhibitor YM976 on the pulmonary mucus secretion of chronic obstructive pulmonary diseases （COPD）. Methods Rat pulmonary mucus hypersecretion was induced by acrolein. Rats treated with or without acrolein were orally administered with YM976 （4. 5 mg/kg） for 12 days. Macrophages were detected by cell count of bronchoalveolar lavage fluid （BALF）. MUCSAC in the lung was detected by RT-PCR and immunohistochemistry. Results YM976 （4.5 mg/kg） significantly attenuated pulmonary MUCSAC expression stimulated by acrolein, and reduced the activation of macrophages in BALF （P〈0. 05）. Conclusion YM976 inhibits pulmonary inflammatory response and pulmonary mucus hypersecretion induced by acrolein.

关 键 词：COPD 粘液高分泌 PDE4 MUC5AC 丙烯醛 

分 类 号：R562.2[医药卫生—呼吸系统]