地塞米松对PI3K／Akt途径及哮喘大鼠气道炎症的调控  

Regulation of dexamethasone on PI3K/Akt signal pathway in asthmatic rat airway inflammation

作　　者：徐慧[1] 戴元荣[1] 夏晓东[1] 何剑波[1] 

机构地区：[1]温州医学院附属第二医院呼吸科,325027

出　　处：《浙江医学》2010年第1期37-39,42,共4页Zhejiang Medical Journal

摘　　要：目的研究大鼠支气管哮喘（简称哮喘）模型PI3K／Akt信号转导途径与Th1／Th2的关系，探讨地塞米松对PI3K／Akt信号转导途径及大鼠气道炎症的调控。方法取SPF级雄性SD大鼠32只，随机分为对照组、哮喘组、地塞米松组、渥曼宁青霉素组，每组8只。以卵白蛋白（OVA）致敏和激发建立大鼠哮喘模型。酶联免疫吸附试验（ELISA）测定BALF中IL-4、IL-12含量；免疫组化MaxvisionTM法测定肺组织中P—Akt蛋白的表达量并观察其表达位置；Western blot测定肺组织匀浆中P—Akt蛋白的含量；并对各检测指标进行组间比较分析。结果（1）与对照组比较，其他3组大鼠IL-4含量显著增高、IL-12含量显著降低（均P〈0.01）；而且地塞米松组及渥曼宁青霉素组IL-4含量显著低于哮喘组、IL-12含量明显高于哮喘组（P〈0.05或0．01）。（2）与对照组比较，其他3组大鼠P—Akt蛋白相对表达量及光密度值均显著增高（均P〈0.01）；而且地塞米松组及渥曼宁青霉素组P—Akt蛋白相对表达量及光密度值均显著低于哮喘组（均P〈0.01）.（3）肺组织中P—Akt蛋白含量与IL-4含量呈显著正相关（r=0．918，P〈001），与IL-12含量呈显著负相关（r=-0．868，P〈0.01）.结论哮喘大鼠模型中出现了PI3K—Akt通路的激活，其Th1/Th2失衡可能与P13K／Akt通路的激活有关。糖皮质激素可能通过抑制PI3K／Akt通路，改善Th1/Th2失衡，从而减轻哮喘气道炎症。Objective To investigate the regulatory role of dexamethason （DXM） on PI3K/Akt（phosphoinositide 3-kinase and Akt）signal pathway in asthmatic rat airway inflammation. Methods Thirty-two male adult Sprague-Dawley （SD） rats were randomly divided into control group （C）, the asthma group （A）,DXM group （D）,Wortmannin group （W）.The asthma model was induced by sensitization with ovalbumin （OVA） and AI（QH）a, and repeat exposure to aerosolized OVA. The concentration of IL-4 and IL-12 in BALF were measured by ELISA method. The expressions of p-Akt protein were detected by immunohistochemistry （IHC）; the level of p-Akt in lung homogenate was measured by Western blot. Results The IL-4 levels in BALF of group A,D and W were significantly higher than those of group C （all P〈0.01）; and those of group A were highest （P〈0.01）. The IL-12 levels in BALF of group C were significantly higher than those of group A, D and W （all P〈0.01）,the levels of group D and W were higher than those of group A （P〈0.01 or P〈0.05）. The expressions of p-Akt protein of lung tissues detected by immunohistochemistry and Western blot in group A, D and W were higher than those of group C （P〈0.01）; while the expressions of group D and W were lower than those of group A （P〈0.01）. Correlative analysis： The expression of p-Akt protein in lung homogenate was positively correlate with IL-4 levels in BALF （r=0.918,P〈0.01）. There were negative correlations of expression of p-Akt protein in lung homogenate with IL-12 levels in BALF （r=-0.868,P〈0.01）. Conclusion The results indicate that Thl/Th2 cytokine might be regulated by PI3K/Akt signal transduction in asthmatic rat model; and glucocorticoids may convert imbalance of Th1/Th2 cytokine and reduce the airway inflammation through inhibition of PI3K/Akt signal transduction.

关 键 词：哮喘 气道炎症 PI3K AKT 糖皮质激素 罗红霉素 

分 类 号：R5[医药卫生—内科学] R562.25[医药卫生—临床医学]