Akt对哮喘小鼠下呼吸道及内脏感觉传入部位IL-1β表达的影响

The Upregulatory Effect of PKB/Akt on IL-1β in the Lower Respiratory Tract and Viscerosensory Afferent Sites of the Asthmatic Mice

目的探讨在哮喘发病机制中,PKB/Akt对哮喘小鼠肺组织及C7-T5段脊神经节和相应节段脊髓后角IL-1β表达的调节作用。方法BALB/c小鼠30只,按随机数字表法均分为正常对照组、哮喘组、PKB/Akt阻断组,免疫组织化学检测各组小鼠肺组织及C7-T5节段脊神经节和相应节段脊髓后角IL-1β的表达,Western blot方法检测各组小鼠肺组织及C7-T5节段脊神经IL-1β的表达。结果免疫组织化学结果显示,哮喘组肺、C7-T5段脊神经节和相应节段脊髓后角IL-1β阳性产物的平均光密度值(MOD)显著高于正常对照组(P<0.01);而PKB/Akt阻断组与哮喘组相比MOD值明显降低(P<0.05)。Western blot结果显示:与正常对照组比较,哮喘组小鼠肺、C7～T5段脊神经中IL-1β的IDV(integrated density value)与β-actin IDV的比值均明显升高(P<0.01),而PKB/Akt阻断组明显低于哮喘组(P<0.05)。结论NGF介导的Akt通路的激活可上调IL-1β的表达,介导哮喘气道高反应和炎症反应。

Objective To study the regulatory effect of PKB/Akt on the expression of IL-1β in the lung, C7 - T5 spinal ganglia and the corresponding spinal dorsal horn of the asthmatic mice. Methods 30 BALB/c mice were randomly divided into normal control group, asthmatic group, the asthmatic mice blocked with LY294002 group on average. The expression of IL-1β was observed by immunohistochemical method and Western blot. Results Immunohistochemistry showed that the mean optic density（MOD） of IL-1β positive product in the lung, spinal ganglia and dorsal horn of C7 - T5 increased significantly in the asthmatic mice than in normal control （ P 〈 0,01）, but decreased in the asthmatic mice blocked with LY294002 than in the asthmatic mice （ P 〈 0.05）. Western blot showed that the ratios of IL-1β integrated density value （ IDV）/β -actin IDV in the lung, C7 - T5 spinal cord increased significantly in the asthmatic mice than in normal control （ P 〈 0.01）, but decreased in the asthmatic mice blocked with LY294002 than in the asthmatic mice （ P 〈 0.05）. Conclusion The upregulation of IL-1β by the activated NGF-mediated Akt pathway might he involved in the asthmatic airway hyperreactivity and inflammation.