HCN2在大鼠外周神经病理性疼痛发生中的作用

doi:10.12047/j.cjap.5574.2017.072

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (4): 294-298.doi: 10.12047/j.cjap.5574.2017.072

HCN2在大鼠外周神经病理性疼痛发生中的作用

黄涛^1,2, 付波^1,2, 王静³, 王滨^1,2, 刘少君^1,2, 翁谢川^1,2

1. 军事医学科学院基础医学研究所神经生物学研究室;
2. 军事医学科学院国家蛋白质组学重点实验室, 北京 100850;
3. 军事医学科学院卫生学环境医学研究所, 天津 300050

收稿日期:2017-03-01 修回日期:2017-06-02 出版日期:2017-07-28 发布日期:2018-06-19
通讯作者: 刘少君,Tel:010-66931304,010-66931345;E-mail:liusj@bmi.ac.cn;翁谢川,E-mail:wengxc2000@sina.com E-mail:liusj@bmi.ac.cn;wengxc2000@sina.com
基金资助:
北京市自然科学基金面上项目（7142123）；蛋白质组学国家重点实验室优青课题（SKLP-YB201403）；总装预研基金课题（9140A26060215JB94001）

Effects of HCN2 in the development of peripheral neuropathic pain in rats

HUANG Tao^1,2, FU Bo^1,2, WANG Jing³, WANG Bin^1,2, LIU Shao-jun^1,2, WENG Xie-chuan^1,2

1. Department of Biology, Institute of Basic Medical Science, Academy of Military Medical Science;
2. State Key Laboratory of Proteomics, Beijing 100850;
3. Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Tianjin 300050, China

Received:2017-03-01 Revised:2017-06-02 Online:2017-07-28 Published:2018-06-19
Supported by:
北京市自然科学基金面上项目（7142123）；蛋白质组学国家重点实验室优青课题（SKLP-YB201403）；总装预研基金课题（9140A26060215JB94001）

摘要/Abstract

摘要： 目的：初步探讨超极化激活的环核苷酸门控通道2型（HCN2）在外周神经病理性疼痛发生中的作用。方法：将24只健康成年大鼠进行随机分组（n=12）：假手术组（Sham）大鼠仅分离左侧L4、L5脊神经，模型组（SNL）分离脊神经后进行相应的结扎处理，手术7 d后用行为学方法进行模型评价；将造模成功的大鼠进行随机分组（n=6）：①阴性对照组（Saline），左侧足底注射生理盐水；②阳性对照组（GBPT），腹腔注射加巴喷丁；③实验组（ZD7288），左侧足底注射HCN非特异性阻断剂ZD7288。在给药前以及给药后1 h、4 h、24 h、48 h用疼痛行为学实验检测其对神经病理性疼痛的作用；分别取手术前对照组（Control）、假手术组（Sham）和模型组（SNL）大鼠的背根神经节（DRG）（n=6），利用qPCR和Western blot的方法研究造模前后大鼠DRG内HCN2的表达的变化情况。结果：①成功建立大鼠神经痛模型；②与Saline组比较，GBPT组和ZD7288组在注射1 h后，均能明显的减轻大鼠神经病理性疼痛的症状（P<0.01），而GBPT组和ZD7288组之间比较则无差异；③与Control组和Sham组相比较，SNL组大鼠DRG内的HCN2 mRNA表达量明显增加（P<0.01）；与Control组和Sham组相比较，SNL组大鼠DRG内的HCN2通道蛋白表达量显著增加（P<0.05）。结论：HCN2参与外周神经病理性疼痛的发生，并有可能成为治疗神经病理性疼痛一个潜在的新靶点。

关键词: 外周神经病理性疼痛, HCN2, 背根神经节, 大鼠

Abstract: Objective: To explore the effects of hyperpolarization-activated cyclic nucleotide-gated channels 2(HCN2) in the formation of peripheral neuropathic pain in rats.Methods: Twenty-four healthy adult rats were divided into two groups randomly(n=12):the sham group rats were only isolated the left L4, L5 spinal nerve, the spinal nerve ligation(SNL) group was separated the spinal nerve and performed the corresponding ligation. The behavioral experiments were tested 7 days after operation; The model rats were randomly divided into 3 groups(n=6):① negative group(Saline), intra-plantar injection of saline in left hindpaws; ② positive group(gabapentin, GBPT), intraperitoneal injection of gabapentin; ③ experimental group(ZD7288), intra-plantar injection of ZD7288 in left hindpaws. The behavioral experiments were tested before injection and 1 h, 4 h, 24 h and 48 h after injection; Obtaining the dorsal root ganglion(DRG) of the control group (before operation), sham group and the SNL group(n=6), using qPCR and Western blot to analyze the mRNA and protein of HCN2 in rats' DRG.Results: The rat model of neuropathic pain was successfully established. Compared with saline group, GBPT group and ZD7288 group could significantly reduce the symptoms of neuropathic pain in rats after injection 1 h (P<0.01), and there was no difference between GBPT group and ZD7288 group. Compared with control group and sham group, the expression of HCN2 mRNA in SNL group's DRG was significantly increased (P<0.01), and the expression of HCN2 channel protein was also increased significantly (P<0.05).Conclusion: HCN2 is involved in the development of peripheral neuropathic pain and is likely to be a potential new target for the treatment of neuropathic pain.

Key words: peripheral neuropathic pain, HCN2, DRG, rat

黄涛, 付波, 王静, 王滨, 刘少君, 翁谢川. HCN2在大鼠外周神经病理性疼痛发生中的作用[J]. 中国应用生理学杂志, 2017, 33(4): 294-298.

HUANG Tao, FU Bo, WANG Jing, WANG Bin, LIU Shao-jun, WENG Xie-chuan. Effects of HCN2 in the development of peripheral neuropathic pain in rats[J]. CJAP, 2017, 33(4): 294-298.

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HCN2在大鼠外周神经病理性疼痛发生中的作用

Effects of HCN2 in the development of peripheral neuropathic pain in rats

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