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纸质出版:2014
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SB202190对卡英酸诱导的癫痫大鼠模型认知功能的影响及机制[J]. 中山大学学报(医学科学版), 2014,35(3).
Effects and Mechanism of SB202190 in Cognition on Model of Kainic Acid-induced Rats[J]. Journal of Sun Yat-sen University (Medical Sciences), 2014, 35(3).
摘 要:【目的】 研究p38丝裂原活化蛋白激酶(p38MAPK)选择性抑制剂SB202190对卡英酸(KA)致痫大鼠学习、记忆能力的影响及其与海马神经元凋亡的关系的探讨。【方法】40只大鼠随机分为4组:假处理组、模型组和SB202190低、高剂量组(剂量分别为7.5 mg/kg,30 mg/kg),对各组大鼠进行行为学观察,应用Morris水迷宫试验,检测大鼠学习和记忆能力,同时通过BL-420F生物机能实验系统描记脑电图的变化,采用 TUNEL 检测细胞凋亡并计算凋亡率,应用免疫组织化学染色及Western-blotting方法检测与凋亡有关的因子:Bcl-2、Bax和Caspase-3。【结果】假处理组无发作;模型组给KA后均出现3 ~ 5级癫痫发作;与模型组相比,低、高剂量SB2021902组发作程度明显减轻,表现为1 ~ 3级;Morris水迷宫试验:定位航行试验:SB202190两个剂量组逃避潜伏期同模型组比较均明显缩短(P< 0.05),以高剂量组显著;空间探索试验:同模型组比较,SB202190两个剂量组第一象限停留时间均延长(P < 0.05),穿环指数均增加(P < 0.05),以高剂量组显著;模型组较假处理组Bax、Caspase-3因子表达明显增强(P< 0.01),同时Bcl-2因子表达明显减弱(P < 0.01),细胞凋亡明显增加,而与模型组比较,SB202190两个剂量组使这些结果发生相反改变(P <0.01)。【结论】 SB202190可以减轻大鼠癫痫发作,提高大鼠的学习和记忆能力,其机制可能与其减少海马神经元凋亡有关,而Bcl-2、Bax和Caspase-3可能在癫痫后神经元凋亡过程中具有重要的作用。
Abstract: 【Objective】 To study the effects of SB202190 on behaviors and abilitiesof learning and memory of epilepsy rats induced by kainic acid and its relationto apoptosis of rat hippocampal neurons. 【Methods】 40 rats were divided into 4 groups:sham group, KA group and two different dose SB202190 pretreated groups. After treatmentwith relevant reagents, the behaviors were observed. The abilities of learning andmemory were evaluated by Morris water maze test. Electrocorticogram was recordedby BL-420F. The number of apoptosis neurons was observedand the apoptosis rate was calculated by TUNEL. Expressions of apoptosis-related factors: Bcl-2, Bax and Caspase-3 were detected by IHC and Western blot. 【Results】 Behavior observationshowed seizure-free in the blank group; the degree of attackwas 3-5 in the KA group while 1-3in the pretreated groups. Compared with KA group, total escape latency was significantlyreduced in SB202190 groups in the positioning navigation trial (P < 0.05), meanwhilesignificantly prolong of first platform quadrant latency and increase of platformcrossing index were observed in SB202190 groups in spatial probe trial (P<0.05),expressly in high dose group. Expressions of Bax and Caspase-3were significantly increased (P < 0.01), expressions of Bcl-2were significantly decreased and the number of cells apoptosis was increased inmodel rats than that of sham group (P < 0.01), but the results were reversed inSB202190 two doses groups than that of model group. 【Conclusion】 SB202190 can reduceattack level of epileptic rats and increase the ability of learning and memory inKA-induced epilepsy rats. The mechanism may be associatedwith apoptosis, Bcl-2, Bax, and Caspase-3 may paly an important role in the process of neuronal apoptosiscaused epileptic.
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