缺氧预处理对创伤性脑损伤大鼠缺氧诱导因子-1α、葡萄糖转运体3型及神经元核蛋白表达的影响  

Effect of hypoxic preconditioning on the expression of hypoxia- inducible factor-1α, glucose transporter-3 and neuron-specific nuclear protein in cerebral cortex in rats with traumatic brain injury

作　　者：武孝刚 刘家传[1] 杨艳艳[1] 王金标[1] 张星[1] 王春琳[1] 周治民[1] 

机构地区：[1]解放军第一〇五医院神经外科,合肥230031

出　　处：《中华神经创伤外科电子杂志》2015年第1期11-15,共5页Chinese Journal Of Neurotraumatic Surgery：Electronic Edition

基　　金：全军医学科技"十二五"科研项目(CWS11J262);2009年南京军区医学科技创新重点课题(09Z009)

摘　　要：目的探讨缺氧预处理(HPC)对创伤性脑损伤(TBI)大鼠挫伤灶周围皮层组织中缺氧诱导因子-1α(HIF-1α)、葡萄糖转运体3型(GLUT-3)表达及神经元存活影响。方法 120只Sprague-Dawley大鼠按随机数字法分为对照组(12只)、TBI组(54只)、HPCT组(54只)。TBI组按Feeney自由落体撞击法建立大鼠TBI模型,HPCT组先给予3 d HPC(50.47 k Pa,3 d,3 h/d),之后同法致伤。采用RT-PCR及Western blotting检测伤后1、4、8、12 h及1、3、7、14 d挫伤灶周围HIF-1α、GLUT-3 m RNA及蛋白的表达,并分析HIF-1α与GLUT-3之间的相关性,采用免疫组化检测伤后14 d挫伤灶周围神经元核蛋白(Neu N)阳性表达率来观察神经元存活情况。多组间比较行单因素方差分析,用LSD法行两两比较分析2组间差异,相关性分析用Pearson相关分析,以P<0.05为差异具有统计学意义。结果 TBI组伤后4 h至3 d HIF-1α、GLUT-3的表达均明显增加(P<0.05)。HPCT组HIF-1α及GLUT-3的表达在伤后1 h即增强,伤后4 h至7 d HIF-1α、GLUT-3表达量和伤后14 d Neu N阳性细胞数均明显高于TBI组,差异均具有统计学意义(P<0.05)。相关性分析表明HIF-1α与GLUT-3 m RNA及蛋白的表达均呈正相关。结论 HPC可通过诱导皮层脑组织HIF-1α的表达,上调GLUT-3 m RNA及蛋白的表达,进而提高TBI后急性期神经元的存活率。Objective To investigate the effect of hypoxic preconditioning （HPC） on the expression of hypoxia-inducible factor-1α, glucose transporter-3 and neuronal survival in cerebral cortex in rats with traumatic brain injury （TBI）. Methods A total of 120 SD rats were randomly assigned to control group （CON, n=12）, traumatic brain injury group （TBI, n=54） and traumatic brain injury after HPC group （HPCT, n=54）. The rats of TBI group were established the TBI model by Feeney free falling dart impact method;The rats of HPCT group were treated with HPC （50.47 kPa, 3 h/d, 3 d） firstly, and then establish the HPCT model by Feeney free falling dart impact method. Detect the expression of HIF-1α、GLUT-3 mRNA and protein around the contusion focus on 1 h, 4 h, 8 h, 12 h, 1 d, 3 d, 7 d, 14 d post-injury by RT-PCR and Western blotting, analysis the relevance between HIF-1αand GLUT-3, observe the neuronal survival situation of NeuN positive expression rate around the contusion focus by immunohistochemistry in 14 d post-injury. Take single factor analysis of variance among groups, analyzed by multiple comparisons with LSD method, correlation analysis with Pearson correlation analysis method, set P〈0.05 as the statistically significant difference. Results TBI group, both HIF-1αand GLUT-3 increased expression significantly on 4 h, 8 h, 12 h, 1 d and 3 d post-injury （P〈0.05）. HPCT group, both HIF-1αand GLUT-3 increased expression on 1h post-injury, the expression of HIF-1αand GLUT-3 on 4 h to 7 d post-injury and the count of NeuN positive cells 14 d post-injury were both significantly higher than TBI group （P〈0.05）. Correlation analysis showed that the expression of HIF-1αand GLUT-3 mRNA and protein were positive correlated. Conclusion HPC can induce the expression of HIF-1αin the cortical brain tissue, raise the expression of GLUT-3 mRNA and protein, and improve the acute neuronal survival rate post-injury of TBI.

关 键 词：脑损伤 创伤和损伤 缺氧诱导因子-1 α亚基 葡萄糖转运体3型 GLUCOSE TRANSPORTER type 3 

分 类 号：R651.15[医药卫生—外科学]