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阿片肽基因在大鼠脑孤束核中的表达及单侧颈迷走神经切断术诱导的增加:对阿片神经元在呼吸控制机制中作用的启示

Opioid peptide gene expression in the nucleus tractus solitarius of rat brain and increases induced by unilateral cervical vagotomy: implications for role of opioid neurons in respiratory control mechanisms.

作者信息

Rutherfurd S D, Gundlach A L

机构信息

University of Melbourne, Department of Medicine, Heidelberg, Vic., Australia.

出版信息

Neuroscience. 1993 Dec;57(3):797-810. doi: 10.1016/0306-4522(93)90025-b.

DOI:10.1016/0306-4522(93)90025-b
PMID:7906015
Abstract

Neurons expressing messenger RNA encoding the opioid peptide precursors, preproenkephalin and preprodynorphin were localized in the medulla oblongata of the rat by in situ hybridization of specific DNA oligonucleotide probes. Neurons containing preproenkephalin messenger RNA were found throughout the medullary reticular formation in the gigantocellular and paragigantocellular reticular nuclei, the parvicellular and lateral reticular nuclei; commissural, medial and ventrolateral subnuclei in the nucleus tractus solitarius and the nucleus of the spinal trigeminal tract. Labelled cells were also concentrated in the more medial regions of the area postrema. In contrast, neurons containing preprodynorphin messenger RNA had a more restricted distribution and were detected in the commissural and ventrolateral nucleus tractus solitarius and nucleus of the spinal trigeminal tract, especially in the more dorsal regions. Expression of preproenkephalin and preprodynorphin messenger RNA was also examined in the dorsal vagal complex of rats that had undergone a unilateral nodose ganglionectomy or cervical vagotomy. Twenty-four hours after both cervical vagotomy and nodose ganglionectomy, there was a specific 1.5-2-fold elevation in preproenkephalin and preprodynorphin messenger RNA levels in the ventrolateral subnucleus of the contralateral nucleus tractus solitarius relative to levels in the ipsilateral nucleus tractus solitarius and in the nucleus tractus solitarius of sham-operated animals. Previous immunohistochemical studies demonstrating the co-localization of enkephalin and dynorphin in the ventrolateral nucleus tractus solitarius suggest that these changes occurred in the same population of neurons. In light of the suggested role of the ventrolateral nucleus tractus solitarius as a central respiratory centre and the activation of the intact pulmonary afferents that innervate this area following a unilateral vagotomy (which increases inspiration volume and expiratory time by affecting the Hering-Breuer reflex), our results suggest a specific involvement of enkephalin- and dynorphin-containing neurons in the ventrolateral nucleus tractus solitarius in central respiratory control mechanisms.

摘要

通过特异性DNA寡核苷酸探针的原位杂交,在大鼠延髓中定位了表达编码阿片肽前体、前脑啡肽原和前强啡肽原信使核糖核酸的神经元。含有前脑啡肽原信使核糖核酸的神经元存在于整个髓质网状结构中,包括巨细胞网状核和旁巨细胞网状核、小细胞网状核和外侧网状核;孤束核的连合、内侧和腹外侧亚核以及三叉神经脊束核。标记细胞也集中在最后区的更内侧区域。相比之下,含有前强啡肽原信使核糖核酸的神经元分布更局限,在孤束核的连合和腹外侧核以及三叉神经脊束核中检测到,尤其是在更靠背侧的区域。还在接受单侧结状神经节切除术或颈迷走神经切断术的大鼠的迷走神经背侧复合体中检测了前脑啡肽原和前强啡肽原信使核糖核酸的表达。在颈迷走神经切断术和结状神经节切除术后24小时,相对于同侧孤束核和假手术动物的孤束核中的水平,对侧孤束核腹外侧亚核中的前脑啡肽原和前强啡肽原信使核糖核酸水平有特异性的1.5至2倍升高。先前的免疫组织化学研究表明脑啡肽和强啡肽在孤束核腹外侧核中共定位,这表明这些变化发生在同一群神经元中。鉴于孤束核腹外侧核被认为是一个中枢呼吸中心,以及单侧迷走神经切断术后支配该区域的完整肺传入神经的激活(通过影响黑林-布雷尔反射增加吸气量和呼气时间),我们的结果表明孤束核腹外侧核中含脑啡肽和强啡肽的神经元在中枢呼吸控制机制中具有特定作用。

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