| 摘要: |
| 目的探讨缺氧诱导因子-1α（HIF-1琢）、BNIP3在蛛网膜下腔出血（SAH）后早期皮层神经元凋亡中的作用机制。方法采用颈内动脉穿刺法建立SAH大鼠模型，设SAH组、2-甲氧雌二醇（2ME2）组和假手术（sham）组，每组10只。造模后24h对SAH大鼠神经功能进行评价；取大鼠脑组织，采用TUNEL法检测凋亡指数，免疫荧光染色检测HIF-1琢的组织细胞定位，Westernblot检测HIF-1α、BNIP3蛋白表达水平。结果与sham组比较，造模后24hSAH组大鼠脑组织中HIF-1琢、BNIP3蛋白表达水平均明显升高（均P＜0.05），凋亡指数明显增高（P＜0.05），神经功能评分明显降低（P＜0.05）。与SAH组比较，2ME2组大鼠脑组织中HIF-1琢、BNIP3蛋白表达水平均明显下降（均P＜0.05），凋亡指数明显下降（P＜0.05），神经功能评分明显升高（P＜0.05）。HIF-1琢主要定位表达于神经元。结论HIF-1琢介导上调BNIP3并参与了SAH后早期皮层神经元凋亡过程。 |
| 关键词: 蛛网膜下腔出血 缺氧诱导因子 -1琢 凋亡 BNIP3 |
| DOI：10.12056/j.issn.1006-2785.2017.39.14.2017-787 |
| 分类号: |
| 基金项目:国家自然科学基金（81171094） |
|
| HIF-1α mediated up-regulation of BNIP3 involving in early cortical apoptosis after subarachnoid hemorrhage |
|
HU Qiang, YU Wenhua, CHEN Gao, DU Quan
|
|
Hangzhou First People's Hospital
|
| Abstract: |
| Objective To investigate the role of hypoxia inducible factor-1α (HIF-1α) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) in early cortical apoptosis after subarachnoid hemorrhage (SAH). Methods Thirty Sprague-Dawley rats were randomly divided into sham, 2-methoxyestradiol (2ME2), and SAH groups with 10 animals in each. The SAH model was induced by endovascular perforation on internal carotid in rats of 2ME2 and SAH groups. The neurological scores were recorded 24h after SAH induced. The expression of HIF-1α and BNIP3 was detected by Western blotting. TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique was adopted to detect apoptotic cell. HIF-1α-positive cells were observed by double fluorescence labeling. Results Compared to sham group, expression of HIF-1α and BNIP3 was
increased, marked cell apoptosis and neurologic function decline were observed in brain tissue of SAH group 24 h after model induced (P ＜0.05). Compared to SAH group, the expression of HIF-1α and BNIP3 was suppressed, cell apoptosis was diminished and neurologic function improved in 2ME2 group (P＜0.05). Double fluorescence labeling showed that HIF-1α was mainly located in neurons. Conclusion These data indicated that HIF-1α-mediated up-regulation of BNIP3 in involved in early cortical apoptosis after subarachnoid hemorrhage. |
| Key words: Subarachnoid hemorrhage Hypoxia-inducible factor-1琢 Apoptosis BNIP3 |
