The Neuroendocrine Modulation Effect On Substance P In The Hypothalamic Paraventricular Nuclei Of Asthma Rat And Its Possible Mechanism

【Objection】To explore the effect of substance P (SP) in Paraventricular nucleus (PVN) in rats on the asthma onset and its possible mechanism in neuroendocrine.【Methods】Male Sprague-Dawley (SD) rats are divided into normal group and asthma group. Rats are sensitized with Ovalbumin (OA) ip. Placed on a stereotaxic frame, the asthmatic rats are inserted a tube into PVN according to the rat brain atlas. After the asthmatic rat are challenged with OA iv, SP and (or) NK1 receptor antagonist S0145 is microinjected into PVN. Then targets on pulmonary function are recorded by Powerlab/400 system. Corticotropin-releasing hormone (CRH) in median eminence (ME), Adrenoeorticotropic hormone (ACTH) and Corticosterone (CORT) in peripheral blood and the content of SP in PVN are detected by the radioimmunoassay method. At the same time, Calcitonin generalated peptide-like immunoreactive (CGRP-IR) positive fibers in airways, Fos positive cells distributed in PVN and Hippocampus are detected by Immunohistochemistry method and glucose-DAB-nickel technique respectively.【Results】1)The contents of SP in PVN and Fos positive neurons in PVN and Hippocampus are presented strongly in asthamatic rats compared with normal group. After rats are injected intravenously OA (8mg·kg-1), the asthma attacks and is about lasting for 60 min. Targets on pulmonary function are changed significantly. EMGdi frenquency,TE /TI and RAW increase, while EMGdi integral ,MVV and cL decrease. The contents of CRH, ACTH and CORT are decreaced. Relatively, CGRP-IR positive fibers increase markedly in the bronchus and lungs compared with normal group 2)After microinjecting 8μg SP into PVN at the onset of asthma, EMGdi frenquency,TE /TI and RAW increase, while EMGdi integral ,MVV and cL decrease. The contents of CRH, ACTH and CORT are decreased simultaneously. CGRP-IR positive fibers in airways increase markedly compared with OA+NS group. 3)After microinjecting 1μg S0145 into PVN at the onset of asthma, changes on pulmonary function that are induced by OA iv could be ameliorated remarkably. The contents of CRH, ACTH and CORT are increaced simultaneously. CGRP-IR positive fibers in airways decrease markedly compared with OA+NS group. 4) If SP is injected into PVN after the microinjection of S0145, the effects of SP will disappear.【Conclusion】This study suggests that SP in PVN could regulate asthma by neuroendocrine pathway, which may be involved with the dscrease of CRH, ACTH, CORT and increase of CGRP release.