哮喘时豚鼠下呼吸道及内脏感觉传入部位 Trk A 的表达以及神经生长因子对其影响

Effect of nerve growth factor on TrkA expression in lower respiratory tract and viscerosensory afferent sites in asthmatic guinea pigs

目的：探讨神经生长因子(NGF)在哮喘发病中的作用及其神经免疫调节机制。方法：应用免疫组织化学方法检测豚鼠下呼吸道和内脏感觉传入部位 NGF 高亲和力受体酪氨酸激酶 A(TrkA),用 Western blot 蛋白印迹方法检测豚鼠肺、脊神经节和脊髓背角 NGF 和 TrkA 的表达。结果：(1)与对照组相比,哮喘豚鼠气道上皮、肺内炎性细胞、血管平滑肌内的神经末梢、C_7～T_5段脊神经节及相应节段脊髓背角内 TrkA 阳性反应产物的平均灰度值均明显降低；哮喘+NGF 抗体组则明显高于哮喘组。(2)哮喘组豚鼠肺、C_7～T_5段脊神经节及相应节段脊髓样品中 TrkA 或 NGF 目标带的 IDV 与内参照 IDV 的比值均明显升高,而哮喘+NGF 抗体组则明显低于哮喘组。结论：NGF 可上调 TrkA 的表达,TrkA 介导的细胞内信号传导系统可能是 NGF 参与哮喘发病的主要途径之一。

Objective： To explore the role and neuroimmune mechanism of nerve growth factor （NGF） in the path- ogenesis of asthma. Methods： The changes of the NGF high-affinity receptor tyrosine kinase A （TrkA） were investigated by immunohistochemistry in lower respiratory tract and viscerosensory afferent sites of the guinea pigs. The expression of NGF and TrkA were observed by Western blot in the lung, spinal ganglia and spinal dorsal horn in all the groups. Results： The mean grey values of TrkA positive products decreased significantly in the lower respiratory tract, nerve terminals in vascular smooth muscle, C7-T5 spinal ganglia and corresponding spinal dorsal horn of the asthmatic guinea pigs compared with the normal saline control group and the simple sensitized group. However, the mean grey values were much higher in NGF antibody group than those in asthmatic group. The ratios between Integrated Density Value （IDV） for TrkA or NGF protein band and IDV for β-actin protein band increased markedly in the lung, C7-T5 spinal ganglia and the corresponding spinal dorsal horn of asthmatic group. However, the rations of NGF antibody group reduced markedly in comparison with asthmatic group. Conclusion： NGF may upregulate the expression of TrkA. The intracellular signal transduction system mediated by TrkA might be one of the main routes for the involvement of NGF in the pathogenesis of asthma.