侧脑室注射肾上腺髓质素增加大鼠心血管相关核团中c-fos的表达并激活脑内一氧化氮神经元(英文)  

Intracerebroventricular administration of adrenomedullin increases the expression of c-fos and activates nitric oxide-producing neurons in rat cardiovascular related brain nuclei

作　　者：季淑梅[1] 王泽民[1] 李学平[2] 何瑞荣[1] 

机构地区：[1]河北医科大学基础医学研究所生理室,石家庄050017 [2]河北医科大学基础医学研究所神经生物室,石家庄050017

出　　处：《生理学报》2004年第3期328-334,共7页Acta Physiologica Sinica

摘　　要：本研究利用Fos蛋白和一氧化氮合酶(nNOS)双重免疫组化方法,观察侧脑室注射肾上腺髓质素(adrenomedullin,ADM)对大鼠心血管相关核团中c-fos表达及一氧化氮神经元的影响,以探讨ADM在中枢的作用部位并研究其在中枢的作用是否有NO神经元参与。侧脑室注射ADM(1 nmol/kg,3 nmol/kg)诱发脑干的孤束核、最后区、蓝斑核、臂旁核和外侧巨细胞旁核,下丘脑的室旁核、视上核和腹内侧核以及前脑的中央杏仁核和外侧缰核等多个部位的心血管中枢出现大量Fos样免疫反应神经元。侧脑室注射ADM(3 nmol/kg)引起脑干的孤束核、外侧巨细胞旁核,下丘脑的室旁核、视上核内的Fos-nNOS双标神经元增加;ADM(1 nmol/kg)亦可引起室旁核、视上核内的Fos-nNOS双标神经元增加,而对孤束核、外侧巨细胞旁核内的Fos-nNOS双标神经元无影响。降钙素基因相关肽(calcitonin gene-related peptide,CGRP)受体拮抗剂CGRP_(8-37)(30 nmol/kg)可明显减弱此效应。以上结果表明,ADM可兴奋脑内多个心血管相关核团的神经元并激活室旁核、视上核、孤束核及外侧巨细胞旁核内的一氧化氮神经元,此效应可能部分由CGRP受体介导。To define the action sites of adrenomedullin (ADM) in the rat brain, and to examine whether neuronal NO may participate in the actions of ADM, the present study was undertaken to examine the effects of i.c.v. administration of ADM on the induction of Fos protein and on nitric oxide-producing neurons in rat brain nuclei involved in cardiovascular regulation, using double immunohistochemical method for Fos and neuronal nitric oxide synthase (nNOS). Following i.c.v. administration of ADM (1 nmol/kg, 3 nmol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the nucleus of the solitary tract (NTS), the area postrema, the locus coeruleus, the parabrachial nucleus and the nucleus paragigantocelluaris laterialis (PGL) in the brainstem, the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the ventromedial hypothalamic nucleus in the hypothalamus, as well as the cental amygdaloid nucleus and the lateral habenular nucleus in the forebrain. Following i.c.v. injection of ADM (1 nmol/kg, 3 nmol/kg), the number of double-labeled neurons for Fos and nNOS was increased in the PVN and SON. Small numbers of double-labeled neurons were also found in the NTS and PGL following i.c.v injection of ADM (3 nmol/kg), while i.c.v. injection of ADM (1 nmol/kg) did not change the number of double-labeled neurons in the NTS and PGL. Pretreatment with calcitonin gene-related peptide receptor antagonist CGRP_(8-37) (30 nmol/kg) significantly reduced the action of ADM (3 nmol/kg) in the brain. These results suggest that centrally administered ADM may increase the expression of c-fos in the forebrain, the hypothalamus and the brainstem and activate nitric oxide-producing neurons in the PVN, SON, NTS and PGL. These effects may be partly mediated by CGRP receptors.

关 键 词：肾上腺髓质素 Fos免疫组织化学反应 降钙基因相关肽受体拮抗剂CGRP8-32 前脑 下丘脑 脑干 一氧化氮 

分 类 号：Q42[生物学—神经生物学]