NGF对哮喘豚鼠下呼吸道及内脏感觉传入部位TNF-α mRNA表达的上调作用

THE UPREGULATIVE EFFECT OF NGF ON THE EXPRESSION OF TNF-α mRNA IN THE LOWER RESPIRATORY TRACT AND VISCEROSENSORY AFFERENT SYSTEM OF THE 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 应用原位杂交方法结合显微图像分析 ,研究实验性哮喘豚鼠下呼吸道和内脏感觉传入部位肿瘤坏死因子 αmRNA(TNF αmRNA)表达的变化以及NGF抗体对其的影响。 结果 生理盐水组与单纯致敏组TNF αmRNA的表达没有显著差异 (P >0 0 5 ) ;与这两个对照组相比 ,哮喘豚鼠TNF αmRNA的表达在气道上皮、肺内炎性细胞、C7～T5段脊神经节及脊髓后角内均明显上调 (P <0 0 1) ;在哮喘 +NGF抗体组 ,上述部位内TNF αmRNA的表达明显低于哮喘组 (P <0 0 1)。 结论 NGF诱发TNF α的表达可能是NGF参与哮喘发病的机制之一 ,NGF抗体抑制哮喘时下呼吸道和内脏感觉传入部位TNF αmRNA的表达可能是治疗哮喘的新途径。

Objective To explore the role and neuroimmune mechanism of nerve growth factor(NGF) in the pathogenesis of asthmatic guinea pigs. Methods By means of in situ hybridization combined with the micro-image analysis to investigate the changes of tumor necrosis factor-α mRNA(TNF-α mRNA) expression and the inhibitory effect of the antibody against NGF in lower respiratory tract and viscerosensory afferent system of experimental asthmatic guinea pigs. Results There was no obvious difference in the expression of TNF-α mRNA between normal saline control group and simple sensitized group(P>0.05).The expression of TNF-α mRNA was significantly upregulated in the lower respiratory tract,C-7-T-5 spinal ganglia and corresponding spinal dorsal horn of the experimental asthmatic guinea pigs compared with the normal saline control group and the simple sensitized group(P<0.01).However,the expressions of TNF-α mRNA in the lower respiratory tract,C-7-T-5 spinal ganglia and corresponding spinal dorsal horn were much lower in NGF antibody group than in asthmatic group (P<0^01).Conclusion The present results indicate that the expression of TNF-α induced by NGF might be one of the mechanisms for the involvement of NGF in the pathogenesis of asthma,and inhibiting expression of TNF-α mRNA in the lower respiratory tract and viscerosensory afferent system with NGF antibody might be a new route for the prevention and treatment of the bronchial asthma.;