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西洛他唑对全脑缺血大鼠学习记忆功能及半胱氨酸天冬酶-3表达的影响

李云,袁晓东,欧阳和中,张轶超,朱美蓉   

  1. 山东大学附属济南市中心医院急诊科, 济南 250013
  • 收稿日期:2006-12-26 修回日期:1900-01-01 出版日期:2008-04-16 发布日期:2008-04-16
  • 通讯作者: 李云

Effects of Cilostazol on the learning and recalling abilities and the caspase-3 expression after global cerebral ischemiareperfusion in rats

LI Yun, YUAN Xiao-dong, OUYANG He-zhong, ZHANG Yi-chao, ZHU Mei-rong   

  1. Department of Emergency, Jinan Central Hospital Affiliated Shandong University, Jinan 250013, Shandong, China
  • Received:2006-12-26 Revised:1900-01-01 Online:2008-04-16 Published:2008-04-16
  • Contact: LI Yun

摘要: 目的研究西洛他唑对全脑缺血大鼠学习记忆功能及半胱氨酸天冬酶-3(caspase-3)表达的影响。方法采用四血管阻断法制作大鼠全脑缺血再灌注模型。将SD大鼠随机分为假手术组(n=8×1)、缺血模型组(n=8×7)和治疗组(n=8×7)。治疗组于缺血前6h和2h各灌胃给予西洛他唑(30mg/kg),以后每隔24h重复给药,其他各组灌胃给予30%二甲基亚砜(30mg/kg)。缺血模型组和治疗组于缺血10min再灌注,6、12、24、48、72h、5d和7d 7个亚组灌注后断头取脑, 采用免疫组织化学方法分析再灌注后不同时间点海马CA1区caspase-3表达水平的变化。另取24只大鼠随机分为假手术组、缺血模型组及治疗组,每个亚组8只。应用Morris水迷宫对全脑缺血再灌注7d的大鼠进行缺血后学习记忆功能的测定。结果caspase-3在假手术组极少见阳性表达;缺血模型组caspase-3的表达于再灌注6h增加,72h达高峰,7d接近正常;治疗组48h、72h、5d和7d亚组caspase-3平均阳性细胞数明显低于缺血模型组(P<0.05);与假手术组比较,5d之中缺血模型组和治疗组平均逃避潜伏期明显延长(P<0.01);与缺血模型组比较,前4d治疗组平均逃避潜伏期明显缩短(P<0.01),第5天两组大鼠的平均逃避潜伏期差异无统计学意义(P>0.05)。结论西洛他唑可以有效地抑制caspase-3升高,这可能是西洛他唑改善缺血大鼠学习记忆功能的机制之一。

Abstract: To explore the effects of Cilostazol on the learning and recalling ability and caspase-3 expression after global cerebral ischemia-reperfusion in rats. MethodsTransient global cerebral ischemia was induced by the fourvessel occlusion in SpragueDawley(SD) rats.SD rats were randomly divided into sham-operated group(n=8×1), model group(n=8×7) and Cilostazol-treating group(n=8×7). Rats in treatment group received two oral administration of cilostazol at 6h and 2h before the global cerebral ischemia,then they were given cilostazol every 24h. Rats in other groups were given the same volume of 30% dimethyl sulfoxide. The rats in model control group and treatment group were decapitated at 6、12、24、48、72h、5d and 7d after 10min cerebral ischemia. The expression of caspase3 in CA1 region of hippocampus were detected by the method of immunohistochemistry. The another 24 rats were randomly divided into 3 groups:shamoperated group(n=8), ischemia reperfusion group (n=8) and treatment group(n=8). They were used to study the learning and recalling ability of rats at 7?d after global ischemia-reperfusion by Morris water maze.Results Caspase-3 was scarecely expressed in shamoperated group;while in model group, it increased at 6 hour, peaked at 72 hour, and deceased nearby to the base lever at 7 day;for caspase-3 mean positive cells in CA1 region, they were obviously lower in 48、72?h、5?d and 7?d subgroups of treatment group than those in model group(P<0.05). Within 5 days, the Escape Latency(EL) in ischemia reperfusion group and treatment group was markedly longer than that of in shamoperated group(P<0.01, P<0.05 respectively);within 4 days, the Escape Latency(EL) in treatment group was markedly shorter than that of in ischemia reperfusion group(P<0.01);whereas on the fifth day,there was no significant difference in these two groups.Conclusion Cilostazol can effectively inhibited the increase of caspase3 levels which may be one mechanism of its increasing the learning and recalling ability of rats.

Key words: phosphodiesterase inhibitors, IschemiaHypoxia, Brain, Reperfusion Injury, Caspase-3

中图分类号: 

  • R743.3
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