Expression of neuropeptides and nitric oxide synthase in neurones innervating the inflamed rat urinary bladder
Expression of neuropeptides and nitric oxide synthase in neurones innervating the inflamed rat urinary bladder
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DOI：
10.1016/s0165-1838(97)00032-5
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发表时间：
1997-07-14
期刊：
影响因子：
--
通讯作者：
Mense, S
中科院分区：
文献类型：
--
作者：
CallsenCencic, P;Mense, S
随着膀胱炎的发展，排尿反射变得过度兴奋。在本研究中的问题是解决，是否在神经肽和一氧化氮合酶（NOS）的表达在神经元通路的膀胱的改变可能参与过度兴奋。用快蓝逆行标记大鼠膀胱背根神经节（DRG）L1、L2、L 6和S1的初级感觉神经元和盆大神经节（MPG）的节后传出神经元。用免疫细胞化学技术检测芥子油引起的膀胱炎症后这些神经元中降钙素基因相关肽（CGRP）、P物质（SP）、甘丙肽（GAL）和一氧化氮合酶（NOS）表达的变化。向膀胱内滴注2.5%芥子油导致膀胱组织大量白细胞浸润，粘膜层部分损伤和逼尿肌反射明显亢进。与对照组动物相比，诱导膀胱炎后48 h，在头侧腰DRG（L1，L2）和腰骶DRG（L 6，S1）中，表达CGRP和SP的FB标记的膀胱传入神经元的比例显著增加（CGRP，+ 15-38%; SP，+47 - 158%）。然而，在两个节段水平上，炎症对膀胱传入纤维中GAL和NOS的表达有不同的影响。显示GAL免疫反应性的FB标记传入神经数量的显著变化主要限于腰骶DRG L 6（+169%）和S1（+60%）。相反，NOS免疫反应性膀胱传入的比例仅在头侧腰DRG L1（+144%）和L2（+193%）中显著增加，而腰骶水平的NOS表达水平不受影响。此外，炎症诱导MPG中表现出NOS免疫反应性的FB标记神经元数量显著增加（+275%）。这些结果表明，CGRP-，SP-，GAL-和NOS-合成的感觉和传出神经元的上调参与急性膀胱炎的反应。由于这些物质在膀胱传入神经中的节段性模式和上调程度的差异，这些物质投射到头侧腰椎和腰骶脊髓，因此建议对交感神经和副交感神经传出神经流出膀胱进行不同的调节。CGRP，SP，GAL和NOS参与调制的兴奋性和抑制性机制，控制膀胱炎引起的逼尿肌反射亢进进行了讨论。(C)1997年Elsevier Science B.V.
Micturition reflexes become hyperexcitable with the development of a cystitis. In the present study the question is addressed, whether alterations in the expression of neuropeptides and nitric oxide synthase (NOS) in the neuronal pathways to the bladder may be involved in the hyperexcitability. Primary sensory neurones in the dorsal root ganglia (DRG) L1, L2, L6 and S1 as well as postganglionic efferent neurones in the major pelvic ganglia (MPG) that innervate the rat urinary bladder were labeled with retrogradely transported Fast Blue (FB). Immunocytochemical techniques were used to determine alterations in the expression of calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL) and NOS in these neurones following mustard oil-induced inflammation of the urinary bladder. Instillation of 2.5% mustard oil into the bladder led to a massive leukocyte infiltration of the vesical tissues, partial damage of the mucosal layer and a marked hyperreflexia of the detrusor muscle. 48 h after induction of the cystitis the proportion of FB-labeled bladder afferent neurones that expressed CGRP and SP were significantly increased in both the rostral lumbar DRGs (L1, L2) and the lumbosacral DRGs (L6, S1) (CGRP, + 15-38%; SP, +47-158%) as compared to control animals. However, there was a differential effect of the inflammation on the expression of GAL and NOS in bladder afferents at the two segmental levels examined. Significant alterations in the number of FB-labeled afferents exhibiting GAL immunoreactivity were mainly restricted to the lumbosacral DRGs L6 (+169%) and S1 (+60%). On the contrary, the proportion of NOS-immunoreactive bladder afferents significantly increased only in the rostral lumbar DRGs L1 (+144%) and L2 (+193%), while the level of NOS-expression was unaffected at the lumbosacral levels. Inflammation furthermore induced a significant increase (+275%) in the number of FB-labeled neurones in the MPGs that exhibited NOS immunoreactivity. These results indicate that an upregulation of CGRP-, SP-, GAL- and NOS-synthesis in sensory and efferent neurones is involved in the response to an acute cystitis. Because of the differences in the segmental pattern and degree of upregulation of these substances in bladder afferents that project to the rostral lumbar and lumbosacral spinal cord a different regulation of the sympathetic and parasympathetic efferent outflow to the urinary bladder is suggested. The involvement of CGRP, SP, GAL and NOS in the modulation of both excitatory and inhibitory mechanisms that control the cystitis-induced detrusor hyperreflexia is discussed. (C) 1997 Elsevier Science B.V.