替尼达普对慢性颞叶癫痫大鼠海马内向整流钾通道2.3亚单位表达的影响  

Effect of Tenidap on expression of inwardly rectifying potassium channel 2.3 in hippocampi of chronic temporal lobe epileptic rats

作　　者：徐岚[1] 吴洵昳[1] 唐兴华[1] 王剑虹[1] 洪震[1] 

机构地区：[1]复旦大学附属华山医院神经内科,上海200040

出　　处：《中华神经科杂志》2010年第7期464-468,共5页Chinese Journal of Neurology

基　　金：高等学校博士学科点专项科研基金资助项目（20070246074）

摘　　要：目的 观察慢性颞叶癫痫（TEE）大鼠致痫后不同时点海马组织中内向整流钾通道（Kir）2.3亚单位mRNA和蛋白的表达变化规律及通道特异性开放剂替尼达普对其表达的影响,探讨Kir2.3通道与TLE发病机制的关系,并为临床应用钾通道开放剂作为抗癫痫药物提供依据.方法 匹罗卡品诱导大鼠产生癫痫持续状态（SE）,持续观察2周,成模为慢性TLE大鼠.用逆转录PCR（RT-PCR）和Western blot方法检测对照组及致痫组大鼠SE终止后0、6、72 h和2周后海马组织中Kit2.3通道mRNA和蛋白表达变化趋势;随后以慢性期2周作为观察时间点,检测替尼达普对大鼠海马Kir2.3通道mRNA及蛋白表达变化的影响.结果 对照组、致痫组SE终止后0、6、72 h和2周时Kir2.3 mRNA/β-actin比值分别为0.080±0.030、0.103±0.045、0.164±0.026、0.132±0.024和0.011±0.008（F：23.684,P〈0.01）;各时间点Kir2.3蛋白/甘油醛-3磷酸脱氢酶（GAPDH）比值分别为0.305±0.030、0.263±0.028、0.767±0.167、0.498±0.077和0.176±0.026（F=44.183,P〈0.05）,其表达呈现急性期增高、慢性期明显降低的动态变化趋势.在慢性期,替尼达普给药组大鼠Kir2.3 mRNA/β-actin与Kir2.3蛋白/GAPDH比值分别为0.021±0.006和0.636±0.140,与未给药组相比表达增高,差异有统计学意义（F=25.216、47.355,P〈0.05、0.01）.结论 Kir2.3通道mRNA和蛋白在慢性期表达下调,可能是难治性癫痫发病的分子生物学机制之一.替尼达普通过增加Kir2.3通道的表达,最终可能减少痫样放电的产生.Objective To observe the change of expression of inwardly rectifying K＋（Kir）2.3 mRNA and protein of Kir in the hippocampus of rats with chronic temporal lobe epilepsy（TLE）in different time points and the effect of Tenidap a Kir2.3 channel opener on its expression,investigate the relationship between Kir2.3 and the pathogenesis of TLE and to explore the potential of Kir agonists as anti-epileptic drugs.Methods The pilocarpine TLE rat model was used.Animals were randomly assigned to the control or the status epilepticus（SE）groups,which were further divided into four time point subgroups consisting of 0.6,72 hours,and 2 weeks post-SE termination.Another subgroup was given Tenidap,a Kir2.3 channel opener,and tested 2 weeks post-SE.Hippoeampi were removed and the expression of Kir2.3 mRNA and protein at different time points was measured by reverse transcription polymerase chain reaction（RT-PCR）and western blotting.Results The ratios of Kir2.3 mRNA and β-actin in normal control and 0,6,72hours and 2 weeks after SE termination were 0.080±0.030,0.103±0.045,0.164±0.026,0.132±0.024.0.011±0.008,respectively（F=23.684,P〈0.01）.The ratios of Kir2.3 protein and GAPDH in propotional groups were0.305±0.030,0.263±0.028,0.767±0.167,0.498±0.077,0.176±0.026（F=44.183.P〈0.05）.The expression of Kir2.3 channel in the epileptic rats was bimodal,increasing immediately after SE,relative to controls,and declining in the chronically epileptic period.Tenidap administration upregulated both the mRNA（0.021±0.006）and protein expression（0.636±0.140） of Kir2.3（F=25.216 and 47.355,P〈0.05 and 0.01）.Condusion These findings suggest that the pathogenesis of TLE is accompanied by a decrease in Kit2.3 expression,which may be ameliorated by the administration of tenidap.

关 键 词：癫痫 颞叶 海马 钾通道 内向整流 吲哚类 

分 类 号：R742.1[医药卫生—神经病学与精神病学]