P物质对哮喘大鼠神经内分泌功能的调节

目的探讨哮喘大鼠脑内P物质在哮喘发作中的作用。方法以大鼠腹腔注射含百日咳和氢氧化铝的卵蛋白溶液制备哮喘动物模型,免疫组织化学方法(SABC)检测哮喘大鼠脑内c-fos蛋白,放射免疫法检测下丘脑室旁核(para-ventricular nucleus,PVN)内P物质(substance P,SP)的含量及正中隆起(ME)中促肾上腺皮质激素释放激素(cortico-tropin-releasing hormone,CRH)和外周血中促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮(corticoster-one,CORT)含量,PVN内分别微量注射外源性SP、SP受体拮抗剂S0145,观察其对哮喘大鼠肺功能与下丘脑-垂体-肾上腺皮质功能轴(hypothalamus-pituitary-adrenal axis,HPA轴)活动的影响。结果哮喘大鼠发作时PVN内SP含量升高;正中隆起CRH与外周血中ACTH、CORT含量均降低(P<0.05),呼/吸时程比和气道阻力增加,膈肌放电积分、肺顺应性减小(P<0.01)。PVN内微量注射SP后哮喘大鼠的肺通气功能进一步下降,CORT、ACTH、CRH含量进一步降低(P<0.01)。SP受体阻断剂S0145则可逆转哮喘发生时大鼠肺功能与HPA轴的改变。结论哮喘大鼠下丘脑室旁核内SP可影响HPA轴的功能,参与哮喘发作。

The role of substance P to modulate the neuroendocrine function in asthmatic rats

Aim To investigate the role of substance P in the brain of asthmatic rats.Methods Rats were injected with aluminum hydroxide and OVA allergens to prepare the animal model of asthma. Then the content of c-fos protein in asthmatic rats' brain was detected by immunohistochemical method (SABC).The content of substance P in paraventricular nucleus (PVN), the content of corticotropin-releasing hormone (CRH) in median eminence (ME), and the content of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in peripheral blood were detected by radioimmunoassay method. Then exogenous SP, SP receptor antagonist S0145 were microinjected in PVN to observe their effect upon lung function and HPA axis in asthmatic rats. Results In asthmatic rats, the content of SP increased within the PVN. The content of CRH, ACTH and CORT decreased (P<0.05).The ratio of expiratory and inspiratory and airway resistance increased. Diaphragm discharge points and lung compliance decreased (P<0.01).After microinject of SP in PVN, there was a further decrease in pulmonary function and the content of CORT, ACTH and CRH in asthmatic rats (P<0.01).While the SP receptor antagonist S0145 might reverse the change of lung function and hypothalamus-pituitary-adrenal axis (HPA axis) in asthmatic rats.Conclusion In asthmatic rats the SP in PVN can affect the function of HPA axis, involved in asthma attacks.