Chen Mao-Hua, Ren Qing-Xian, Yang Wen-Fa, Chen Xiang-Lin, Lu Chuan, Sun Jun
Department of Neurosurgery, The Second Hospital of Wenzhou Zhejiang 325000, China.
Int J Clin Exp Pathol. 2013 Oct 15;6(11):2312-22. eCollection 2013.
Hypoxia-inducible factor 1-alpha (HIF-1α) is a subunit of HIF-l and thought to be able to protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. This study aimed to investigated whether recombinant adenovirus vector over-expressing HIF-lα could affect apoptosis-related proteins (Bcl-2 and Bax) and vascular endothelial growth factor (VEGF) in a rat spinal cord injury (SCI) model. A total of 60 male SD rats were divided into 4 groups: Sham, Control, Ad-Blank and Ad-HIF-1α groups. 1, 3, 7, 14, 28 days after surgery, the behavioral recovery was evaluated with BBB scales. Then, rats were sacrificed and the spinal cord was collected for detection of Bcl-2, Bax and VEGF expressions by immunohistochemistry. Results showed the Bcl-2, Bax, VEGF and HIF-lα expressions increased in animals with SCI, but the increase in Bcl-2, VEGF and HIF-lα expressions were higher in Ad-HIF-1α group when compared with other groups, but Bax expression decreased significantly. In addition, administration of Ad-HIF-1α significantly reduced apoptotic cells and promoted the recovery of neurological function. In conclusion, administration of Ad-HIF-1α after SCI could ameliorate neuronal apoptosis and promote angiogenesis in rats. Our study provides a basis for further exploration of the relationship between HIF1α and SCI.
缺氧诱导因子1α（HIF-1α）是HIF-1的一个亚基，被认为在缺血和缺氧条件下能够保护缺氧细胞免于凋亡或坏死。本研究旨在探讨过表达HIF-1α的重组腺病毒载体是否会影响大鼠脊髓损伤（SCI）模型中凋亡相关蛋白（Bcl-2和Bax）以及血管内皮生长因子（VEGF）。总共60只雄性SD大鼠被分为4组：假手术组、对照组、腺病毒空载体组和腺病毒HIF-1α组。术后1、3、7、14、28天，用BBB评分评估行为恢复情况。然后，处死大鼠并收集脊髓，通过免疫组织化学检测Bcl-2、Bax和VEGF的表达。结果显示，SCI动物中Bcl-2、Bax、VEGF和HIF-1α的表达增加，但与其他组相比，腺病毒HIF-1α组中Bcl-2、VEGF和HIF-1α的表达增加更高，而Bax表达显著降低。此外，给予腺病毒HIF-1α可显著减少凋亡细胞并促进神经功能恢复。总之，SCI后给予腺病毒HIF-1α可改善大鼠神经元凋亡并促进血管生成。我们的研究为进一步探索HIF1α与SCI之间的关系提供了依据。
