AMPK介导上调Bim在大鼠蛛网膜下腔出血后早期皮层神经元凋亡中的作用

目的研究AMP激活的蛋白激酶（AMPK）信号通路在蛛网膜下腔出血（SAH）大鼠脑组织中的表达，探讨AMPK参与SAH早期脑损伤中细胞凋亡的机制。方法血管内穿刺法建立SAH模型，免疫组化检测AMPK与磷酸化AMPK（p-AMPK）的组织细胞定位，RT—PCR及Westernblot检测造模后6、24、48、72h额底皮质AMPKmRNA及P—AMPK、Bim、caspase-3蛋白的动态表达，并与正常对照组和假手术组比较。侧脑室给予AMPK激动剂AICAR及抑制剂CompoundC，检测药物干预对大鼠神经行为及凋亡相关蛋白表达的影响，并与SAH组及vehicle组进行比较。结果SAH后AMPKa...

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Published in西安交通大学学报（医学版） Vol. 34; no. 6; pp. 704 - 709
Main Author 安吉洋 周丽丽 宋锦宁 罗显华 程毛锋 孙鹏 庞宏刚
Format Journal Article
LanguageChinese
Published 西安交通大学医学院,第一附属医院神经外科,陕西西安,710061%西安交通大学医学院,第二附属医院普通外科,陕西西安,710004 2013
Subjects
AMPK
Bim
大鼠
早期脑损伤
细胞凋亡
蛛网膜下腔出血
细胞凋亡
AMPK
大鼠
早期脑损伤
蛛网膜下腔出血
Bim
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ISSN1671-8259
DOI10.7652/jdyxb201306002

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Summary:目的研究AMP激活的蛋白激酶（AMPK）信号通路在蛛网膜下腔出血（SAH）大鼠脑组织中的表达，探讨AMPK参与SAH早期脑损伤中细胞凋亡的机制。方法血管内穿刺法建立SAH模型，免疫组化检测AMPK与磷酸化AMPK（p-AMPK）的组织细胞定位，RT—PCR及Westernblot检测造模后6、24、48、72h额底皮质AMPKmRNA及P—AMPK、Bim、caspase-3蛋白的动态表达，并与正常对照组和假手术组比较。侧脑室给予AMPK激动剂AICAR及抑制剂CompoundC，检测药物干预对大鼠神经行为及凋亡相关蛋白表达的影响，并与SAH组及vehicle组进行比较。结果SAH后AMPKa的mRNA表达升高，p-AMPK、Bim、caspase-3蛋白表达均持续升高；AICAR可以增高AMPK磷酸化和Bim、caspase-3表达水平，加重神经功能缺损，CompoundC可以减低AMPK磷酸化和Bim、caspase-3表达水平，改善神经功能评分。结论AMPK信号通路参与了SAH后早期脑损伤中神经元细胞凋亡的病理生理过程，其机制可能与调控Bim的转录活性有关，抑制AMPK信号通路可以减轻SAH后皮层神经元凋亡。
Bibliography:AN Ji-yang1 , ZHOU Li-li2 , SONG Jin-ning1 , LUO Xian-hua1 , CHENG Mao-feng1 , SUN Peng1 , PANG Hong-gang1 （1. Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi＇an Jiaotong University, Xi＇an 710061~ 2. Department of General Surgery, the Second Affiliated Hospital, Medical School of Xi＇an Jiaotong University, Xi＇an 710004, China）
Objective To investigate the activation of AMP-activated protein kinase （AMPK） and Bim in rat cortex after subarachnoid hemorrhage （SAH） and to explore the role of AMPK in cortical apoptosis in early brain injury after SAH. Methods SAH model was established by an endovascular perforation technique. The immunohistochemical method was used to detect the localization of AMPK and phosphorylated AMPK. RT-PCR was performed to detect the dynamic mRNA expression of AMPKa, and Western blot was used to detect the protein levels of phosphorylated AMPK and apoptosis-related proteins （Bim and caspase-3） in the cortex. After AICAR and compound C were administered via i.
ISSN:1671-8259
DOI:10.7652/jdyxb201306002