张凡喜;张健民;黄晓龙;周玉峰;陈鹏;

• 1:解放军第三二四医院神经外科

摘要(Abstract)：

目的探讨Dickkopf-1(DKK-1)在脑出血大鼠神经元凋亡中的作用及机制。方法采用随机数字法将40只成年雄性SD大鼠分成对照组(n=13)、假手术组(n=13)及脑出血组(n=14)。通过颅内注射自体外周血制作脑出血模型。采用平衡木行走实验和肌力测验进行脑出血模型评估,并利用Real-time PCR和Western blot检测大鼠脑组织中Bcl-2、Bax、p-Akt、Akt及DKK-1蛋白和mRNA表达水平。分离培养原代大鼠皮质神经元,分为对照组、空载体组、DKK-1过表达组、BTBD10(Akt磷酸化激活剂)过表达组,检测细胞中DKK-1表达水平和Akt磷酸化水平,利用流式细胞术检测各组细胞凋亡。结果脑出血组大鼠平衡木行走得分高于对照组和假手术组(P<0.05),而肌力测验评分低于对照组和假手术组(P<0.05)。与对照组和假手术组比较,大鼠脑出血部位脑组织Bcl-2表达降低(P<0.05),而Bax表达则升高(P<0.05),p-Akt表达水平下降(P<0.05),DKK-1表达水平上升(P<0.05)。DKK-1过表达组神经元凋亡率及p-Akt表达水平均高于空载体组和对照组(均P<0.05)。Akt磷酸化激活剂BTBD10过表达组p-Akt水平、Bcl-2蛋白表达高于对照组和空载体组,而Bax蛋白表达则低于对照组和空载体组。BTBD10过表达组神经元存活率高于对照组和空载体组(均P<0.05),且BTBD10和DKK-1共转染组大鼠神经元存活率高于DKK-1转染组(P<0.05)。结论 DKK-1可能通过抑制Akt的磷酸化促进出血性脑卒中大鼠神经元的凋亡。

关键词(KeyWords)： 脑出血;DKK-1;细胞凋亡;Akt

Abstract:

Keywords:

基金项目(Foundation): 中国人民解放军神经创伤防治重点实验室2013年开放课题资助项目(NTP2013005);; 国家科技惠民计划项目(2013GS500101-15)

作者(Author): 张凡喜;张健民;黄晓龙;周玉峰;陈鹏;

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