代谢型谷氨酸受体4通过Rab5抑制神经病理性痛  

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

作　　者：陈锐[1] 王华[1] 江伟[1] 

机构地区：[1]上海交通大学附属第六人民医院麻醉科,上海200233

出　　处：《上海交通大学学报（医学版）》2014年第2期139-143,共5页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金青年科学基金(81100825)~~

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（500nm01）10μL，2次／d×7d，注药前和注药后30min测量其50％PWT。最后，末次给药后1h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1～6d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＋VU0t55041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。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 lh 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 RabSA and Rab5C were significantly higher than those of control group and SNL ＋ VU0155041 group （P 〈 0. 05）,and the differences of activation of mGluR4 and Ran5C Rab5B expression among three groups were

关 键 词：代谢型谷氨酸受体4 Rab5 神经病理性痛 

分 类 号：R741.05[医药卫生—神经病学与精神病学]