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实验性结肠炎对脊髓传入神经元中降钙素基因相关肽和香草酸受体1表达的调节

杨霞, 韩俊庆, 刘然

山东大学附属山东省立医院肿瘤研究治疗中心.山东,济南 250021；山东大学附属齐鲁医院核医学科.山东,济南 250021

摘要

该文旨在探讨肠道局部炎症对脊髓肠道感觉传入神经通路的近期及远期效应，应用三硝基苯磺酸（trinitrobenzencsulfoni acid,TNBS）建立大鼠结肠炎动物模型，用DiI（3）逆行神经标记法识别支配肠道炎症部位的脊髓背根神经节（dorsal root ganglia,DRG）神经元，通过肉眼观察、平均组织损伤评分及髓过氧化物酶活性测定等方法评价肠道组织的炎症反应状态，用免疫组织化学法测定香草酸受体1（vanilloid receptor 1，VR1）和降钙素基因相关肽（calcitonin gene--related pepfide，CGRP）在支配结肠炎症部位的DRG神经元中的表达，比较炎症不同阶段（给予TNBS后7、21、42d）CGRP和VR1阳性神经元的数目。结果显示，炎症急性期（即给予TNBS后7d）结肠黏膜肉眼可见明显损伤，同时相应DRG中表达CGRP及VR1的神经元增加近2倍[（95.38±9.45）％vs（42.86±5.02）％，（89.23±8.21）％vs（32.54±4.58）％]。给予TNBS后21、42d，肠道炎症反应已完全消退，但表达CGRP及VR1的DRG神经元数目仍明显高于对照组[（86.25±8.21）％，（68.28±7.12）％vs（42.86±5.02）％；（67.22±6.52）％，（56.25±4.86）％vs（32.54±4.58）％]。结果提示，肠道局部炎症可以上调支配肠道的脊髓传入神经元中CGRP和VR1的表达，这种异常表达可以持续至肠道炎症反应消退后的一定时间。

关键词： 炎症; 背根神经节; 降钙素基因相关肽; 香草酸受体 1

Effects of experimental colitis on the expressions of calcitonin gene--related peptide and vanilloid receptor 1 in rat spinal cord sensory neurons

Yang Xia, Han Junqing, Liu Ran

Department of Cancer Research and Treatment Center, Shandong Provincial Hospital,Shandong University.Jinan 250021,Shandong；China

Abstract

To study the acute and long-term effects of local gut inflammation on the sensitivity of the spinal sensory neurons, the expressions of vanilioid receptor 1 （VR1） and calcitonin gene-related peptide （CGRP） in the colon-innervated primary sensory neurons in dorsal root ganglia （DRG） were examined in rats with trinitrobenzenesulfonic acid （TNBS）-induced experimental colitis. The neurons projecting to the distal colon were identified by DiI（3） retrograde labelling. Macroscopic examination, mean damage score and myeloperoxidase （MPO） activity were determined to assess the inflammatory status of the colon tissue. The number of CGRP and VR1 immunoreactive neurons at different stages of inflammation （on days 7, 21 and 42 after TNBS treatment） were compared. On day 7 after TNBS treatment, macroscopic damage of the mucosa could be easily detected and the percentage of colon-innervated DRG neurons expressing CGRP and VR1 increased nearly two folds respectively [（95.38±9.45）% vs （42.86±5.02）% for CGRP, （89.23±8.21 ）% vs （32.54±4.58）% for VR1]. When the colon inflammatory reaction was resolved on days 21 and 42 after TNBS treatment, the percentage of colon-innervated DRG neurons expressing CGRP and VR1 were still higher than that in the control group [（86.25± 8.21）%, （68.28± 7.12）% vs （42.86±5.02）% for CGRP; （67.22±6.52）%, （56.25±4.86）% vs （32.54±4.58）% for VR1]. These results suggest that the local gut inflammation increases the expressions of CGRP and VR1 in gut-innervated DRG sensory neurons. More importantly, this abnormal status persists even after the gut inflammatory reaction has been resolved for certain time.

Key words: Inflammation;Dorsal root ganglia;Calcitonin gene-related peptide;vanilloid receptor1

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引用本文：

杨霞, 韩俊庆, 刘然. 实验性结肠炎对脊髓传入神经元中降钙素基因相关肽和香草酸受体1表达的调节[J]. 生理学报 2008; 60 (1): 143-148.

Yang Xia, Han Junqing, Liu Ran. Effects of experimental colitis on the expressions of calcitonin gene--related peptide and vanilloid receptor 1 in rat spinal cord sensory neurons. Acta Physiol Sin 2008; 60 (1): 143-148 (in Chinese with English abstract).