p53 may play an orchestrating role in apoptotic cell death after experimental subarachnoid hemorrhage
p53 may play an orchestrating role in apoptotic cell death after experimental subarachnoid hemorrhage
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DOI：
10.1227/01.neu.0000249287.99878.9b
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发表时间：
2007-03-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, John H.
中科院分区：
文献类型：
--
作者：
Cahill, Julian;Calvert, John W.;Zhang, John H.
目的：对蛛网膜下腔出血（SAH）后继发性脑损伤的了解很少。因此，几乎没有治疗选择。因此，SAH与高发病率和死亡率相关。为了解决这些问题，研究了SAH后全脑细胞凋亡的作用。特别地，研究了p53和三个主要凋亡级联的作用，半胱天冬酶依赖性和半胱天冬酶非依赖性级联以及线粒体途径。Plymouth Meeting，PA）团体。单丝穿刺模型用于诱导SAH，随后在24和72小时处死动物。Western印迹分析，组织学，生理参数，末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记，和免疫组织学技术被用来证明的作用，p53和凋亡级联反应在大鼠脑SAH后。此外，根据死亡率和神经系统结局scores.RESULTS：我们发现，p53和相关的凋亡蛋白上调SAH后，细胞凋亡的下游介质的Pifithrin-α抑制p53的负面影响。此外，我们发现，细胞凋亡抑制导致细胞死亡较少，并在治疗animals.CONCLUSION：这些结果表明，细胞凋亡可能是一个重要的原因，在脑细胞死亡后SAH和p53可能发挥协调作用，关于SAH细胞凋亡。
OBJECTIVE: Secondary brain injury after subarachnoid hemorrhage (SAH) is poorly understood. As a result, there are few treatment options. Consequently, SAH is associated with a high rate of morbidity and mortality. In an effort to combat these problems, the role of apoptosis was examined in the whole brain after SAH. In particular, the role of p53 and the three major apoptotic cascades were studied, the caspase-dependent and caspase-independent cascades and the mitochondrial pathway.METHODS: In this study, 195 Sprague-Dawley rats were divided into three groups, including sham, nontreatment, and treatment (Pifithrin-alpha; BIOMOL, Inc., Plymouth Meeting, PA) groups. The monofilament puncture model was used to induce SAH and the animals were subsequently sacrificed at 24 and 72 hours. Western blot analysis, histology, physiological parameters, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling, and immunohistological techniques were used to demonstrate the role of p53 and the apoptotic cascades in the rat brain after SAH. In addition, outcome was determined based on mortality rates and neurological outcome scores.RESULTS: We found that p53 and associated apoptotic proteins were up-regulated after SAH and that downstream mediators of apoptosis were negatively influenced by the inhibition of p53 by Pifithrin-alpha. Furthermore, we found that apoptotic inhibition resulted in less cell death and an overall favorable outcome in the treated animals.CONCLUSION: These results suggest that apoptosis may be an important cause of cell death in the brain after SAH and that p53 may play an orchestrating role regarding apoptosis in SAH.