戊四氮点燃腺苷A1受体敲除小鼠脑内P-糖蛋白的动态表达变化  

Expression of P-glycoprotein in adenosine A1 receptors knock-out mice after pentylenetetrazol-kindled epilepsy

作　　者：单萍[1] 康慧聪[2] 刘志广[2] 李巷[2] 朱遂强[2] 

机构地区：[1]武汉市第一医院,武汉430022 [2]华中科技大学同济医学院附属同济医院

出　　处：《内科急危重症杂志》2014年第4期273-276,共4页Journal of Critical Care In Internal Medicine

基　　金：国家自然科学基金青年基金项目(No:81201006)

摘　　要：目的:观察戊四氮(PTZ)点燃腺苷A1受体敲除小鼠脑内P-糖蛋白(PGP)的动态表达变化,评价腺苷A1受体在难治性癫痫治疗中的作用。方法:采用腹腔注射PTZ制备慢性点燃癫痫模型,将动物分为野生型组(40只)和敲除鼠组(40只),再根据有无接受点燃及点燃后不同时间点再分为点燃前和点燃后24 h、7 d、30 d亚组,采用RTPCR法、免疫荧光组织化学法观察各组小鼠大脑皮层和海马PGP的表达情况。结果:PTZ点燃后24 h,野生型组小鼠大脑皮层和海马PGP的表达与点燃前比较无显著统计学差异(P>0.05),敲除鼠组PGP的表达显著高于点燃前(P<0.05),2组小鼠点燃后7 d和30 d时PGP的表达均显著高于对照组(均P<0.05),且点燃后30 d PGP显著高于7 d(P<0.05);点燃后7 d时显著高于24 h时(P<0.05),说明PTZ点燃后PGP的表达随时间延长而增高;敲除鼠组PTZ点燃后同一时间点PGP的表达均显著高于野生型组(均P<0.05)。结论:腺苷A1受体激活可下调PGP的表达,调控腺苷系统功能紊乱可能成为治疗耐药性癫痫的新方法。Objective ： To observe the changes of expression of P-glycoprotein （PGP） in adenosine A1 receptors knock- out mice after pentylenetetrazol-kindled epilepsy and evaluated the role of adenosine A1 receptors in the treatment for intrac- table epilepsy. Methods： The animals were divided into wild type （WT） group （40 cases） and adenosine A1 receptors knock-out （KO） group （40 cases）. RT-PCR and immunohistofluorescence were adopted to observe the transcriptional level and protein expression of PGP respectively in cortex and hippocampus of mice subjected to the pentylenetetrazol （PTZ）-in- duced kindling of seizures at 24 hours, 7 days and 30 days post-kindling or mormal ones in two groups. Results ： Twenty-four hours post-kindling, there was no significant difference in the transcriptional level and protein expression of PGP between PTZ-kindled mice and normal ones in WT group （ P 〉 0.05 ）, while the transcriptional level and protein expression of PGP in PTZ-kindled mice were significantly higher than that in normal ones in KO group （ P 〈 0.05 ）. Seven days and 30 days post- kindling, the transcriptional level and protein expression of PGP 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 PGP in PTZ-kindled mice increased with the time went on and there were significant difference 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 PGP in PTZ-kindled mice in KO group were significantly higher those that in WT group at the same time points post-kindling. Conclusion ： The activation of a- denosine A1 receptors decrease the transcriptional level and protein expression of PGP and regulating the system of adenosine dysfunction may be a new treatment method for intractable epilepsy.

关 键 词：腺苷A1受体 戊四氮 P-糖蛋白 难治性癫痫 

分 类 号：R742.1[医药卫生—神经病学与精神病学]