摘要： 目的 探讨5-羟色胺（5-HT）在小鼠慢性背根神经节压迫（CCD）模型中的作用机制。方法 将L型不锈钢棍插入小鼠右侧L₃和L₄椎间孔，持续压迫背根神经节（DRG）建立小鼠CCD模型。在CCD手术前1 d及手术后1、3、5、7 d向小鼠胫骨前区皮内注射10 μL 5-HT （低剂量浓度为0.003 g/L，高剂量浓度为0.3 g/L）后，录像分析小鼠对注射5-HT后所产生的痒与痛行为学；免疫荧光实验检测小鼠DRG中H4蛋白的表达；实时PCR检测CCD模型小鼠压迫5 d后双侧L₃和L₄ DRG内5-HTr1a和5-HTr2a的表达。结果 与手术前1 d比较，低浓度5-HT在CCD手术后3 d可以明显增加痒行为；高浓度5-HT在CCD手术后1 d可以明显增加痒行为（P<0.05）。与手术前1 d比较，低浓度5-HT在小鼠CCD手术后1 d和3 d可以明显增加痛行为（P<0.05）；高浓度5-HT在小鼠CCD手术后1 d可以明显增加痛行为（P<0.05）。与对侧DRG比较，压迫5 d的DRG中H4蛋白，5-HTr1a、5-HTr2a mRNA表达均显著升高（均P<0.05）。结论 受压迫DRG神经元H4、5-HTr1a和5-HTr2a表达上调，引起感受野对5-HT诱发痛与痒的敏化。

5-羟色胺在小鼠慢性背根神经节压迫模型中的作用机制

王涛, 陶金, 方烨红, 崔欢, 马超

中国医学科学院基础医学研究所, 北京协和医学院基础学院人体解剖与组织胚胎学系, 北京 100005

收稿日期:2020-12-04出版日期:2021-06-30发布日期:2021-05-28
通讯作者:马超E-mail:machao@ibms.cams.cn
作者简介:王涛(1980-),男,助理研究员,博士.
基金资助:国家自然科学基金（81771205）；中国医学科学院医学与健康科技创新工程协同创新团队项目（CIFMS#2017-I2M-4-005（TW））


关键词: 5-羟色胺, 小鼠, 慢性背根神经节压迫, 疼痛, 痒
Abstract: Objective To investigate the mechanism of 5-hydroxytryptamine(5-HT) in the chronic compression of dorsal root ganglion (CCD) in mice. Methods An L-shaped stainless steel rod was inserted into the L₃ and L₄ intervertebral foramen on the right side of each CCD model mouse,establishing continuous compression of the dorsal root ganglion(DRG). For this behavioral experiment,model mice were divided into two groups. All mice received an initial intradermal injection of 10 μL 5-HT. Subsequently,the low dose group received 0.003 g/L,and the high-dose group received 0.3 g/L injections into the anterior tibial region 1 day before the CCD operation,and 1, 3,5,and 7 days after the operation. Itching and pain response behaviors after 5-HT injection were analyzed by video recording,and H4 protein expression in the DRG region was detected by immunofluorescence. RT-PCR was used to detect 5-HTr1a and 5-HTr2a expression in bilateral L 3 and L₄ DRG of CCD model mice over 5 days. Results Low dose 5-HT significantly increased itching behavior 3 days after CCD relative to 1 day before,and high dose 5-HT significantly increased itching behavior by 1 day after CCD. Low dose 5-HT significantly increased pain response behavior at 1 and 3 days post-CCD relative to 1 day before CCD,and high dose 5-HT significantly increased pain response behavior at 1 day after CCD. Compared with expression in contralateral DRG,H4 protein expression and 5-HTr1a and 5-HTr2a mRNA expression were significantly increased after 5 days of compression in compressed DRG. Conclusion Expression of H4 protein, and 5-HTr1a and 5-HTr2a mRNA is upregulated in compressed DRG neurons,which sensitizes the receptive field to 5-HT induced pain and itching.
Key words: 5-hydroxytryptamine, mice, chronic dorsal root ganglion compression, pain, itching
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