p53在蛛网膜下腔出血小鼠脑皮质的表达及其与PI3K/Akt信号通路的关系  

Expression of p53 and its relationship with PI3K/Akt signal pathway in subarachnoid hemorrhage in mice cortex

作　　者：李晓晖[1] 李冉[1] 田艳霞[1] 崔颖[2] 崔建忠[3] 王凯杰[3] 高俊玲[1,4] 

机构地区：[1]河北联合大学基础医学部,河北唐山063000 [2]河北医科大学临床医学系,石家庄050017 [3]唐山市工人医院神经外科,河北唐山063000 [4]河北省煤矿卫生与安全实验室,河北唐山063000

出　　处：《解剖学报》2011年第4期446-450,共5页Acta Anatomica Sinica

基　　金：河北省自然科学基金资助项目(C2009001247);河北省教育厅重点课题资助项目(ZH200803);卫生部人类疾病比较医学重点实验室开放课题资助项目(ZDS200801)

摘　　要：目的探讨p53蛋白在实验性蛛网膜下腔出血小鼠脑皮质的表达及其与PI3K/Akt信号通路的关系。方法将72只小鼠随机平均分为3组,即假手术组(Sham组),蛛网膜下腔出血组(SAH组),抑制剂LY294002组(LY组)。采用线栓法制备小鼠蛛网膜下腔出血模型,术后观测6个时相点:0h、3h、6h、9h、12h、24h。用免疫组织化学法观察p53、p-Akt蛋白的表达及分布情况,RT-PCR技术检测皮质p53、p-Akt mRNA水平,Westernblotting检测皮质p53、p-Akt蛋白表达情况。结果 Sham组p53有微量表达;与Sham组相比,SAH组的损伤侧脑半球皮质p53蛋白水平增加,6h达高峰,之后开始回落。SAH组的p-Akt表达在3h开始增加,并持续至24h。LY组p-Akt表达明显低于SAH组(P<0.05),p53则高于SAH组(P<0.05)。Western blotting与免疫组织化学结果一致。结论小鼠蛛网膜下腔岀血后早期p53及p-Akt表达增加;PI3K/Akt信号通路通过调控p53的表达,在小鼠蛛网膜下腔出血后起到脑保护作用。Objective To explore the expression of p53 protein and its relationship with the PI3K/Akt signal pathway in subarachnoid hemorrhage （SAH）. Methods SAH was induced in mice by puncture of internal carotid artety. Seventy-two male mice were randomly divided into sham group, SAH group, LY （ SAH ＋ LY294002） group. The animals were sacrified at 0, the 3rd, the 6th, the 9th, the 12th and the 24th hour, to observe the expression of p53 and p- Akt in the brain with immunohistochemisty and Western blotting. The morphological changes of the neurons were studied by light microscope. RT-PCR was preformed for detecting the expression change of p53 and p-Akt mRNA. Results Neurons in the hippocampal CAI region after SAH showed typical apoptotic features under light microscope. The expression of p53 and p-Akt protein was higher in SAH group than in sham group. Compared with SAH group, the expression of p-Akt decreased while the p53 was increased with the extension of time in LY group. Conclusion p53 and p-Akt are increased in cerebral cortex of mice after SAH. PI3K/Akt signal pathway could protect the brain neurons by modulating the p53 expression, which could induce the cell apoptosis.

关 键 词：蛛网膜下腔出血 P53 Akt 免疫组织化学 免疫印迹法 小鼠 

分 类 号：R743.35[医药卫生—神经病学与精神病学]