戊四氮点燃腺苷A1受体敲除小鼠大脑皮层及海马多药耐药相关蛋白1的动态表达变化  

Dynamic expression of multidrug resistance-associated protein 1 in cortex and hippocampus of mice with adenosine A1 receptors knock-out after pentylenetetrazol-kindled epilepsy

作　　者：张继龙[1] 笱玉兰[2] 罗利俊[2] 单萍[2] 康慧聪[3] 朱遂强[3] 

机构地区：[1]武汉市第一医院急诊科,湖北武汉430022 [2]武汉市第一医院神经内科,湖北武汉430022 [3]华中科技大学同济医学院附属同济医院神经内科,湖北武汉430030

出　　处：《新乡医学院学报》2015年第3期199-204,共6页Journal of Xinxiang Medical University

基　　金：国家自然科学基金青年项目(编号:81201006)

摘　　要：目的观察戊四氮(PTZ)点燃腺苷A1受体敲除小鼠大脑皮层及海马多药耐药相关蛋白1(MRP1)的动态表达变化,评价腺苷系统在耐药性癫痫治疗中的作用,探索耐药性癫痫治疗新思路。方法采用实验小鼠腹腔注射PTZ制备慢性点燃癫痫模型,动物先分为野生型组(n=40)和敲除鼠组(n=40),2组实验动物再根据有无接受点燃及点燃后不同时间点又各自分为点燃前、点燃后24 h、7 d、30 d 4个亚组,分别采用反转录聚合酶链反应、免疫荧光组织化学法检测各组(亚组)小鼠大脑皮层和海马MRP1表达情况。结果 PTZ点燃后24 h时,野生型组小鼠大脑皮层和海马MRP1表达与点燃前比较差异无统计学意义(P>0.05),敲除鼠组小鼠MRP1表达显著高于点燃前(P<0.05),2组小鼠点燃后7、30 d时MRP1表达均显著高于点燃前(P<0.05);2组小鼠大脑皮层和海马MRP1表达点燃后30 d时显著高于点燃后7 d时,点燃后7 d时显著高于点燃后24 h时(P<0.05),PTZ点燃后MRP1表达随时间延长而增高;PTZ点燃后同一时间点(点燃后24 h、7 d、30 d)敲除鼠组MRP1表达均显著高于野生型组(P<0.05)。结论腺苷A1受体激活可下调MRP1表达,调控腺苷系统功能紊乱可能成为治疗耐药性癫痫新的方法。Objective To observe the changes of expression of multidrug resistance-associated protein 1（ MRP1） in cortex and hippocampus of mice with adenosine A1 receptors knock-out after pentylenetetrazol（ PTZ）-kindled epilepsy and evaluate the role of adenosine system in the treatment for drug-resistance epilepsy. Methods The mouse model of PTZ-kindled epilepsy was induced by intraperitoneal injection of PTZ. The mice were divided into wild type（ WT） group（ n = 40） and adenosine A1 receptors knock-out（ KO） group（ n = 40）,then the mice in the two groups were divided into four subgroup： before pentylenetetrazol-kindled group,24 h post-kindling group,7 days post-kindling group and 30 days post-kindling group. Reverse transcription-polymerase chain reaction and immunohistofluorescence were adopted to observe the transcriptional level and protein expression of MRP1 in cortex and hippocampus of mice respectively. Results Twenty-four hours post-kindling,there was no significant difference in the transcriptional level and protein expression of MRP1 between PTZ-kindled mice and normal ones in WT group（ P〉0. 05）,while the transcriptional level and protein expression of MRP1 in PTZ-kindled mice were significantly higher than those in normal ones in KO group（ P〈0. 05）. Seven days and 30 days post-kindling,the transcriptional level and protein expression of MRP1 in PTZ-kindled mice were significantly higher than those in normal ones in both WT and KO groups（ P〈0. 05）. The transcriptional level and protein expression of MRP1 in PTZ-kindled mice increased with the time went on and there were significant differences among 24 hours,7 days and 30 days post-kindling in both WT and KO groups（ P〈0. 05）. The transcriptional level and protein expression of MRP1 in PTZ-kindled mice in KO group were significantly higher than those in WT group at the same time points post-kindling. Conclusion The activation of adenosine A1 receptors can decrease the transcriptional level and protein expression of M

关 键 词：腺苷A1受体 戊四氮 多药耐药相关蛋白1 耐药性癫痫 

分 类 号：R742.1[医药卫生—神经病学与精神病学]