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作 者:陈永平[1] 谢运兰[2] 王衡[3] 陈阳美[1]
机构地区:[1]重庆医科大学附属第二医院神经内科,重庆400010 [2]重庆医科大学附属第二医院中心实验室,重庆400010 [3]汉中市中心医院神经内科,陕西汉中723000
出 处:《南方医科大学学报》2013年第4期528-532,共5页Journal of Southern Medical University
基 金:国家自然科学基金(81171225);重庆市卫生局重点医学科研项目(2010-1-36)~~
摘 要:目的研究沉默信号调控因子1(SIRT1)在难治性癫痫患者及癫痫大鼠颞叶脑组织中的表达与活性,探讨其与癫痫发生发展的关系。方法在难治性癫痫患者及氯化锂-匹罗卡品癫痫大鼠颞叶脑组织中,应用蛋白免疫组织化学、免疫印迹技术检测其表达情况,应用SIRT1去乙酰化活性检测试剂盒检测其活性。结果蛋白免疫组化结果显示:SIRT1主要表达于人与大鼠神经元细胞浆中,且癫痫组SIRT1的表达明显强于对照组。蛋白免疫印迹及活性检测结果显示:相对于非癫痫患者脑组织,SIRT1表达及活性在难治性癫痫患者颞叶脑组织中均明显升高(P<0.05);相对于正常对照组大鼠,SIRT1表达在癫痫动物模型中点燃后的6 h、24 h、72 h、7 d、14 d、30 d、60 d均显著升高(P<0.05),SIRT1活性在6 h、24 h、72 h、7 d、14 d显著升高(P<0.05),其表达与活性的峰值同时出现在72 h。结论癫痫患者及动物颞叶脑组织中上调的SIRT1的表达与活性提示其可能在难治性癫痫发病机制中起重要作用。Objective To investigate the expression and activity of silent information regulator 1(SIRT1) in the temporal lobe of epileptic patients and rat models and explore its role in the occurrence and progression of epilepsy.Methods The temporal lobe tissue of epileptic patients and rat models(induced by lithium-pilocarpine) were examined for SIRT1 expression using immunohistochemistry and Western blotting and also for SIRT1 activity using SIRT1 Deacetylase Assay Kit.Results Immunohistochemistry detected positive SIRT1 expression mainly in the cytoplasm of the neurons in both human and rat brains,and the epileptic groups showed stronger SIRT1 immunoreactivity than the control group.Western blotting and activity assay showed that the expression and activity of SIRT1 were significantly increased in the temporal lobe of patients with refractory epilepsy as compared with the tissues samples from non-epileptic patients(P0.05).In the rat models of epilepsy,SIRT1 expression was up-regulated at 6,24,and 72 h and at 7,14,30,and 60 days after kindling(P0.05) and SIRT1 activity was significantly increased at 6,24,and 72 h and at 7 and 14 days(P0.05),with the peak level of SIRT1 expression and activity occurring at 72 h.Conclusion Up-regulation of SIRT1 expression and activity in the temporal lobe of epileptic patients and rat models may play an important role in the pathogenesis of epilepsy.
关 键 词:沉默信号调控因子1 癫痫 脑组织 突触重塑 神经保护
分 类 号:R742.1[医药卫生—神经病学与精神病学]
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