上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

代谢型谷氨酸受体4通过Rab5抑制神经病理性痛

陈 锐，王 华，江 伟   

  1. 上海交通大学附属第六人民医院麻醉科， 上海 200233
  • 出版日期:2014-02-28 发布日期:2014-03-25
  • 通讯作者: 江 伟, 电子信箱: jiangw@sjtu.edu.cn。
  • 作者简介:陈 锐（1988—）， 女， 硕士生; 电子信箱: cryourfriend@163.com。
  • 基金资助:

    国家自然科学基金青年科学基金（81100825）

Suppressive effect of metabotropic glutamate receptor 4 on neuropathic pain by Rab5

CHEN Rui, WANG Hua, JIANG Wei   

  1. Department of Anesthesiology, the Sixth People′s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
  • Online:2014-02-28 Published:2014-03-25
  • Supported by:

    Young Scientists Project of National Natural Science Foundation, 81100825

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摘要：

目的 探讨代谢型谷氨酸受体4 （mGluR4）激活后抑制神经病理性痛的机制。方法 首先取24只SD大鼠，鞘内置管后随机分为空白对照组（n=6)、假手术组（n=6)和脊神经根结扎（SNL）组（n=12)。空白对照组只行鞘内置管术，其余大鼠均于术前和术后第1～6日测量50%机械缩足阈值（50%PWT）；其次，将SNL组大鼠于术后第7日起，随机分为SNL+生理盐水组（n=6）和SNL+VU0155041组（n=6），分别予以鞘内注射生理盐水和VU0155041 （500 nmol）10 μL，2次/d×7 d，注药前和注药后30 min测量其50%PWT。最后，末次给药后1 h取空白对照组、SNL+生理盐水组和SNL+VU0155041组大鼠左侧脊髓腰膨大处送检基因芯片并利用Western blotting检测mGluR4及Rab5各亚型的表达变化。结果 SNL大鼠术后1～6 d其手术同侧后肢50%PWT较空白对照组及假手术组明显降低（P<0.01）；SNL+VU0155041组大鼠手术同侧后肢50%PWT与SNL+生理盐水组相比自给药第4日起逐渐升高（P<0.01）；Agilent表达谱基因芯片结果显示：SNL+生理盐水组的Rab5含量高于空白对照组，而空白对照组和SNL+VU0155041组相比无明显差异；Western blotting结果显示：SNL+生理盐水组的mGluR4表达明显低于空白对照组和SNL+VU0155041组（P<0.05），而Rab5A和Rab5C的表达明显高于空白对照组和SNL+VU0155041组（P<0.05），Rab5B在3组中的表达差异无统计学意义（P>0.05）。结论 mGluR4激活后可能是通过Rab5A和Rab5C调控突触囊泡递质释放从而影响神经病理性痛。

关键词: 代谢型谷氨酸受体4, Rab5, 神经病理性痛

Abstract:

Objective To explore the mechanism of neuropathic pain suppression by activating metabotropic glutamate receptor 4 (mGluR4). Methods Firstly, 24 SD rats were randomly divided into blank control group (n=6), shame operation group (n=6), and SNL group (n=12) after intrathecal catheterization. Rats in control group were only undergone the intrathecal catheterization. Values of 50%PWT were measured for other rats before surgery and 1~6 d after surgery. Then, rats in SNL group were randomly divided into SNL+saline group (n=6) and SNL+VU0155041 group (n=6) and received intrathecal injection of saline and VU0155041(500 nmol) 10 μL twice a day for seven days, respectively. Values of 50%PWT were measured before injection and 30 min after injection. Finally, left spinal dorsal horn of the spinal enlargement of control group, SNL+saline group and SNL+VU0155041group were obtained 1h after last injection and submitted for gene chip examination. The expression of mGluR4 and the subtypes of Rab5 were determined by Western blotting. Results During 1~6 d after surgery, values of 50%PWT of ipsilateral hindpaws in SNL group were significantly lower than those of the blank control group and shame operation group （P<0.01); the values of 50%PWT of the ipsilateral hindpaws in SNL+VU0155041 group were gradually higher than those of SNL+saline group from the forth day after injection (P<0.01); and the results of Agilent gene chip showed that Rab5 in SNL+saline group was higher than that of control group, while control group has no difference with SNL+VU0155041 group. The expression of mGluR4 in SNL+saline group was significantly lower than that of control group and SNL+VU0155041 group （P<0.05）, but the expression of Rab5A and Rab5C were significantly higher than those of control group and SNL+VU0155041 group （P<0.05), and the differences of Rab5B expression among three groups were not statistically significant （P>0.05). Conclusion The activation of mGluR4 can affect neuropathic pain by regulating neurotransmitter release of synaptic vesicles through Rab5A and Ran5C.

Key words: metabotropic glutamate receptor 4, Rab5, neuropathic pain