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.