酸敏感离子通道阻断剂对酸诱导偏头痛模型小鼠的影响  

Effect of Acid-sensing Ion Channels Blocker on Acid Induced Migraine Mice Model

作　　者：康玉琪 陈康[1] 何小华[2] 尹皓[1] 毛立武[3] 卢祖能[1] 肖哲曼[1] 

机构地区：[1]武汉大学人民医院神经内科,武汉430060 [2]武汉大学基础医学院病理生理教研室,武汉430060 [3]随州市中心医院神经内科,武汉441300

出　　处：《神经损伤与功能重建》2016年第1期5-8,共4页Neural Injury and Functional Reconstruction

基　　金：国家自然科学基金(No.81471133;30900459);湖北省卫计委重点项目(No.WJ2015MA007);高等学校博士学科点专项科研基金课题(No.200804861046);湖北省自然科学基金(No.2014CFB734);武汉市科技局2015年应用基础研究计划项目(No.2015060101010047)

摘　　要：目的:观察酸敏感离子通道阻断剂对酸诱导偏头痛模型小鼠行为学及相关蛋白表达的影响。方法:24只小鼠随机分为p H7.4组、p H6.0组、阿米洛利治疗组、Pc Tx1治疗组,每组6只。p H7.4组采用p H值7.4的合成组织间液(SIF)涂抹硬脑膜,后3组采用p H值6.0的SIF建立小鼠实验性偏头痛模型,阿米洛利治疗组、Pc Tx1治疗组分别给予阿米洛利和Pc Tx1治疗。观察小鼠制模后1 h内挠头次数、3 h后三叉神经脊束核尾侧亚核内c-fos及脑干中酸敏感离子通道(ASIC1a)蛋白的表达。结果:在造模后1 h内p H6.0组的挠头次数明显多于p H7.4组(P<0.01),阿米洛利治疗组和Pc Tx1治疗组则明显少于其他两组(P<0.01)。与p H7.4组相比,p H6.0组的小鼠脑干中三叉神经脊束核尾侧亚核内的c-fos免疫反应阳性细胞数明显增多(P<0.01);阿米洛利治疗组和Pc Tx1治疗组与p H6.0组相比,相应部位c-fos免疫反应阳性细胞数明显减少(P<0.01)。与p H7.4组相比,p H 6.0组脑干中的ASIC1a蛋白表达较高(P<0.05);阿米洛利治疗组、Pc Tx1治疗组与p H6.0组相比,ASIC1a蛋白表达均明显下调(P<0.01)。结论:酸敏感离子通道阻断剂能够减少偏头痛模型小鼠行为学异常及相关蛋白表达,提示酸敏感离子通道参与偏头痛的发生机制。Objective： To observe the effect of acid-sensing ion channels （ASICs） blocker on ethology and related protein expression of acid induced migraine mice model. Methods： Twenty-four mice were randomly divided into groups pHT.4, pH6.0, amiloride, PcTxl （n=6 in each group）. The dura mater of the pH7.4 group was daubed by pH7.4 synthetic interstitial fluid （SIF）. And the dura mater of the other three groups were daubed by pH6.0 SIF to induce headache. The groups Amiloride and PcTxl were given amiloride or PcTxl for treatment respectively. The number of scratching head was counted within t h after building model. The expressions of c-los in the caudal spinal trigeminal nucleus （cSTN） and ASICla in the brain stem were observed 3 h later. Results： The number of scratching head of the pH6.0 group was obviously more than that of the pH7.4 group （P〈0.01）. The number of scratching head of the groups amiloride and PcTxl were obviously less than the other two groups （P〈0.01）. Com- pared with the pH7.4 group, the number of c-los immunoreactive positive cells ofpH6.0 group was significantly in- creased in the caudal spinal trigeminal nucleus of mice （P〈0.01）. Compared with the pH6.0 group, the numbers of c-fos immunoreactive positive cells of amiloride group and PcTxl group were significantly decreased （P〈0.01）. Compared with the pH7.4 group, the ASICla expression ofpH6.0 group was higher in the brain stem of mice （P〈 0.05）. Compared with the pH6.0 group, the ASIC l a expressions of amiloride group and PcTxl group were signifi- cantly lower （P〈0.01）. Conclusion： That ASICs blocker could reduce behavior abnormalities of migraine mice model and the expression of related protein suggests ASICs involved in the mechanism of migraine.

关 键 词：阿米洛利 PcTx1 偏头痛 C-FOS ASIC1a 

分 类 号：R741[医药卫生—神经病学与精神病学]