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mRNA expression and activity of ADAM17 in hippocampus after chronic cerebral hypoperfusion:experiment with aged rats
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- Author:
- No author available
- Journal Title:
- NATIONAL MEDICAL JOURNAL OF CHINA
- Issue:
- 35
- DOI:
- 10.3760/j.issn:0376-2491.2007.35.018
- Key Word:
- 脑缺血;分解素类;金属内肽酶类;认知障碍
Abstract： 目的 探讨α-分泌酶在脑缺血后认知障碍发生机制中的作用.方法 将48只老龄Wistar大鼠随机分为低灌注组和假手术组,每组细分为术后1、2、4及16周4个亚组.永久性阻断大鼠双侧颈总动脉构建脑慢性低灌注模型;用Y迷宫测试大鼠学习记忆能力;用荧光定量PCR法检测大鼠海马α-分泌酶ADAM17 mRNA表达;用直接荧光法检测海马α-分泌酶活性.结果 低灌注组术后2、4及16周Y迷宫测试成绩均显著下降.术后2、4和16周低灌注组α-分泌酶ADAM17 mRNA表达(与参照物比值分别为0.78±0.03、0.78±0.02和0.54±0.03)显著低于假手术组(分别为1.12±0.05、0.99±0.04和1.01±0.04),差异有统计学意义(均P＜0.01);而低灌注组α-分泌酶活性则于术后1、2、4和16周(荧光值分别为33 880±1086、37 496±817、32 295±864和30 069±1111)持续性显著降低,与假手术组(分别为39 497±838、39 802±1052、40 137±776和39 894±1076)相比,差异有统计学意义(均P＜0.01).结论 脑慢性低灌注下调海马组织α-分泌酶ADAM17 mRNA表达并抑制α-分泌酶活性,推测可能因此增加了α-分泌酶作用底物APP的量,间接激活APP代谢的β-分泌酶途径,最终增加脑内Aβ的生成量,进而损害大鼠学习记忆能力.
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