TrkA对哮喘小鼠下呼吸道气道阻力及IL-1β表达的上调作用

The Upregulation of TrkA on Airway Resistance in the Lower Respiratory Tract and the Expression of IL-1β in the Asthmatic Mice

目的研究NGF的特异性高亲合力受体TrkA对哮喘小鼠下呼吸道气道阻力及IL-1β的表达的调节作用,探讨TrkA介导的信号通路在哮喘发病机制中的作用。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、TrkA抗体阻断组。利用An iRes2005肺功能仪测小鼠气道阻力,利用免疫组织化学方法测定IL-1β表达,M etamoph图象分析系统对结果进行分析。结果哮喘小鼠吸气阻力和呼气阻力明显高于正常组小鼠(P<0.01),TrkA组吸气阻力和呼气阻力明显低于哮喘组。免疫组织化学结果显示TrkA抗体阻断组肺(0.324±0.013)、C7-T5节段脊神经节(0.301±0.065)及对应的脊髓后角(0.216±0.019)IL-1β免疫阳性产物平均光密度值明显低于哮喘组小鼠(0.796±0.025、0.745±0.016、0.528±0.011,P<0.01)。结论NGF介导的TrkA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 nerve growht factor （NGF） specific highly affinity receptor TrkA on the airway resistance of lower respiratory tract and the expression of IL-1 β in the asthmatic mice to explore the function of TrkA mediated signal pathway in the asthmatic pathogenesis. Methods 30 BALB/c mice were randomly divided into normal control group, asthmatic group, anti-TrkA group on average. The airway resistance of mice was measured with AniRes2005 pulmonary function meter, and the alterations of IL-1β immunoreactivity were investigated by immunohistochemical method and analyzed by Metamoph analysis system. Results Inspiratory resistance and expiratory resistance in the asthmatic mice are obviously higher than those in normal control mice, but ebviously lower in anti-TrkA group than in the asthmatic mice. The mean optic density（MOD） of IL-1β positive substance in lung（0. 324 ±0.013）and C7-T5 spinal ganglionic neurons （0.301 ±0. 065） ）and corresponding posterior horn of spinal cord （0.216 ±0.019） in the asthmatic mice blocked with TrkA-antibody is lower than those in the asthmatic mice （0.796 ±0.025,0.745 ±0.016,0.528 ±0.011, P 〈 0. 01）. Conclusion The expression of IL-1β was upregulated by the activated NGF mediated TrkA pathway,which might be involved in the asthmatic airway hyporreactivity and inflammation.