甲强龙对吸烟大鼠气道磷酸二酯酶_(4D)(PDE_(4D))表达的影响

Effect of Methylprednisolone on expression of phosphodiesterase_(4D) (PDE_(4D)) in rat airways after cigarette inhalation.

目的探讨甲强龙对吸烟大鼠气道粘膜上皮磷酸二酯酶4D(PDE4D)表达的影响及机制。方法烟雾吸入建立大鼠慢性支气管炎模型,低剂量和高剂量干预组大鼠香烟吸入之前分别给予腹腔内注射甲基强的松龙1mg/kg和10mg/kg,均1次/d。采用免疫组化检测气管及肺气道上皮PDE4D表达的变化,以灰度扫描和图像分析测定PDE4D阳性染色的平均吸光度;收集支气管肺泡灌洗液(BALF)进行细胞计数及分类;ELISA检测BALF中IL-8(interleukin-8)和TNF-α(tumor necrosis factor-α)浓度的变化。结果与对照组相比,吸烟显著增加大鼠气管与肺气道粘膜上皮PDE4D的表达,且PDE4D阳染增加与BALF中IL-8和TNF-α释放量增加呈正相关。甲强龙干预后,PDE4D蛋白阳染减低,BALF中释放减少。以上差异均具有统计学意义(P<0.05)。结论PDE4D在香烟诱导的大鼠慢性支气管炎气道粘膜上皮中呈高表达;甲强龙可抑制大鼠气道上皮PDE4D高表达,同时气道炎性细胞的生成及IL-8和TNF-α的释放均减少;甲强龙通过抑制PDE4D的表达在慢性气道炎症中发挥重要作用。

Objective To explore the mechanism of methylprednisolone on expression of phosphodiesterase4D （ PDE4D ） in rat airways membranous epithelia after smog inhalation（cigarette tar 17mg, nieotinamide 1.4mg ） and methylpredniselone intervention. Methods The rat airways chronic bronchitis model was established by cigarette inhalation, intraperitoncaly injected with methylprednisolone in two intervention groups before exposing to cigarette smog（respectively at the dose of 1mg/kg, qd and at the dose of 10mg/kg, qd）. The proteins expression of PDE4D in trachea and lung samples was determined by immunohistochemical staining. The average optical density Of positive staining PDE4D was determined by image analysis technique and gray scale scanning;Cells counting and classification were carried out through collection of BALF, and the concentrations of IL-8 and TNF-α in BALF were detected by ELISA. Results Compared with control group, the expression of PDE4D was obviously elevated in tracheal and lung samples of immunohistochemical staining in cigarette inhalation group （P 〈 0.05 ）. Moreover, the increased the positive staining rate of PDE4D was positively correlated with the increased release of IL-8 and TNF-α in BALF.The expression of positive PDE4D staining and the release of IL-8 and TNF-α in BALF were decreased after the treatment with methylprednisolone（ P 〈 0.05）. Conclusion PDE4D show over-expression in cigarette-induced rat airways chronic bronchitis. The over-expression of PDE4D in rat airways epithelia may be inhibited by methylprednisolone, meanwhile which may reduce the creation of inflammation cells in rat airways and the release IL-8 and TNF-α in BALF. Methylprednisolone exerted and important function though restraining the expression of PDE4D in chronic airways inflammation.