Pinacidil抑制线粒体和死亡受体通路减少大鼠脑缺血再灌注后神经元凋亡(英文)

被引:21
作者
张鸿 [1 ]
宋利春 [1 ]
刘艳艳 [2 ]
马英 [1 ]
吕永利 [3 ]
机构
[1] 中国医科大学附属盛京医院神经内科
[2] 天津市天和医院脑系科
[3] 中国医科大学基础医学院解剖教研室
关键词
pinacidil; glipizide; 脑缺血; 凋亡; ATP敏感性钾通道; 线粒体; 死亡受体; 信号通路; caspase-3; caspase-8; caspase-9;
D O I
暂无
中图分类号
R743 [脑血管疾病];
学科分类号
1002 ;
摘要
目的探讨ATP敏感性钾通道开放剂pinacidil对大鼠脑缺血再灌注后神经元凋亡的保护作用及信号转导机制。方法 100 只Wistar 雄性大鼠随机分为四组:A 组(假手术组)、B组 (缺血组)、C 组 (KATP开放剂处理组)及D组 (KATP开放剂和阻断剂处理组)。用线栓法制备大鼠大脑中动脉缺血(middle cerebral artery occlusion,MCAO)模型,用DNA断端末端标记法(terminal-deoxynucleotidytransferase-mediated dUTP-biotin nick end labeling,TUNEL)检测神经元凋亡,用原位杂交方法检测caspase-3、caspase-8及caspase-9 mRNA的表达。结果 (1) C组12 h、24 h、48 h、72 h 时间点的凋亡细胞数较 B、D 组显著减少(P<0.05 或 P<0.01) ;B 组和 D组之间无显著性差异(P>0.05)。(2) C 组 caspase-3 mRNA 和 caspase-8 mRNA 在各时间点及 caspase-9 mRNA 在 12 h、24 h、48 h、72h 时间点的表达显著少于B组和D组(P<0.01或P<0.05),B组和D组之间无显著性差异(P>0.05)。结论 KATP通道开放剂能显著减少大鼠脑缺血再灌注后的细胞凋亡及caspase-3、caspase-8及caspase-9 mRNA的表达。KATP通道开放剂可能通过抑制线粒体通路和死亡受体通路降低神经元凋亡,保护缺血再灌注损伤后的脑组织。
引用
收藏
页码:145 / 150
页数:6
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