Zhuang Zong, Zhao Xudong, Wu Yi, Huang Renqiang, Zhu Lin, Zhang Yang, Shi Jixin
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, P.R. China.
Ann Clin Lab Sci. 2011 Fall;41(4):364-72.
The serine-threonine kinase Akt plays an important role in survival pathways by inactivating downstream apoptogenic factors in many cell systems. In the following study, we investigated whether or not the activation of the Phosphatidylinositol 3-kinase (PI3K)-Akt pathway could reduce neuronal apoptosis following subarachnoid hemorrhage (SAH). Rats were randomly divided into 6 groups: control group, SAH group, SAH+ saline group, SAH+ vehicle group, SAH+ Insulin-like Growth Factor 1 (IGF-1) group, and SAH+Ly294002 (PI3K pathway inhibitor) group. All SAH animals were subjected to injection of autologous blood into the cisterna magna twice (on day 0 and on day 1). The administration was executed via cerebral ventricle 30 minutes before the induced SAH on day 0 and was continued every 24 hours for 72 hours. Whole brains were obtained on day 2. Phospho-Akt (pAkt) expression was analyzed by immunohistochemistry and western blotting. The neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL). We found that the PI3K-Akt pathway was activated in the brain after experimental SAH. Moreover, administration of IGF-1 significantly elevated pAkt expression and decreased the percentage of apoptotic neurons following SAH, while administration of Ly294002 suppressed pAkt expression and induced increased neuronal apoptosis following SAH. Taken as a whole, our results suggested that the activation of PI3K-Akt pathway could mediate the protective effect against neuronal apoptosis after SAH.
丝氨酸 - 苏氨酸激酶Akt通过使许多细胞系统中的下游凋亡因子失活，在生存途径中发挥重要作用。在以下研究中，我们调查了磷脂酰肌醇3激酶（PI3K）-Akt途径的激活是否可以减少蛛网膜下腔出血（SAH）后的神经元凋亡。大鼠被随机分为6组：对照组、SAH组、SAH + 生理盐水组、SAH + 赋形剂组、SAH + 胰岛素样生长因子1（IGF - 1）组和SAH + Ly294002（PI3K途径抑制剂）组。所有SAH动物均接受两次向小脑延髓池注射自体血（在第0天和第1天）。给药在第0天诱导SAH前30分钟通过脑室进行，并每24小时持续给药72小时。在第2天获取全脑。通过免疫组织化学和蛋白质印迹分析磷酸化Akt（pAkt）表达。通过末端脱氧核苷酸转移酶介导的尿苷5'-三磷酸 - 生物素缺口末端标记（TUNEL）评估神经元凋亡。我们发现实验性SAH后大脑中的PI3K - Akt途径被激活。此外，给予IGF - 1可显著提高pAkt表达，并降低SAH后凋亡神经元的百分比，而给予Ly294002可抑制pAkt表达，并诱导SAH后神经元凋亡增加。总体而言，我们的结果表明PI3K - Akt途径的激活可以介导对SAH后神经元凋亡的保护作用。
