缺氧预处理诱导创伤性脑损伤大鼠皮层组织HIF-1α及GLUT-1表达的影响  

Effect of hypoxic preconditioning on expressions of hypoxia-inducible factor-1αand Glucose transporter-1 in the cerebral cortex of rats with traumatic brain injury

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

机构地区：[1]安徽医科大学解放军临床学院附属解放军第一○五医院神经外科,合肥230031

出　　处：《中华神经医学杂志》2014年第4期366-370,共5页Chinese Journal of Neuromedicine

基　　金：全军医学科技“十二五”科研面上项目（CWS11J262）;2009年军区医学科技创新重点（092009）

摘　　要：目的研究缺氧预处理（HPC）对创伤性脑损伤（TBI）大鼠挫伤区周围皮层脑组织缺氧诱导因子-1α（HIF-1α）及葡萄糖转运蛋白-1（GLUT-1）表达的影响。方法102只SD大鼠按随机数表法分为对照组（C组：n=6）、创伤性脑损伤组（TBI组：n=48）、缺氧预处理后创伤性脑损伤组（HPCT组：n=48）。HPCT组大鼠先置于低压氧舱行缺氧预处理（50．47kPa，3h／d，3d），而后HPCT组和TBI组采用自由落体打击法建立大鼠创伤性脑损伤模型。伤后分别于1、4、8、12h和1、3、7、14d处死大鼠留取皮层脑组织标本，并分别采用RT—PCR和Westernblotting检测挫伤周围皮层HIF—1α及GLUT-1的表达情况。结果与对照组比较，TBI组伤后4h、8h、12h、1d及3dHIF-1α和GLUT-1的表达均明显增加，差异有统计学意义（P〈0．05）；伤后1h、7d及14dHIF-1α和GLUT-1的表达较对照组差异无统计学意义（P〉0．05）。HPCT组与对照组和TBI组比较，HIF-1α和GLUT-1的表达在伤后1h即开始增加，伤后4h、8h、12h、1d、3d及7d均明显增加，差异有统计学意义（P〈0．05）；伤后14dHIF-1α和GLUT-1的表达对照组和TBI组差异无统计学意义（黔0．05）。结论缺氧预处理可提高创伤性脑损伤后脑组织的缺氧耐受性，并通过调整脑内葡萄糖代谢通路发挥脑保护作用．其机制可能与诱导皮层脑组织HIF-1α的表达，进而上调GLUT-1mRNA及蛋白的表达有关。Objective To investigate the effect of hypoxic preconditioning （HPC） on the expressions of hypoxia-inducible factor-1α（HIF-1α） and Glucose transporter-1 （GLUT-1） in cerebral cortex of rats with traumatic brain injury （TBI）. Methods One hundred and two SD rats were randomly assigned to control group （n=6）, TBI group （n=48） and TBI after HPC group （HPCT, n=48）. The rats of HPCT group were exposed to 50.47 kPa absolutely for 3 h daily for consecutive 3 days; 24 h after the last precondition, the TBI models in the rats of HPCT group and TBI group were established with restricted free fall injury method. At each time point （1, 4, 8 and 12 h, and 1, 3, 7 and 14 d after TBI）, 6 rats from TBI group and HPCT group were sacrificed respectively. The brain tissues were prepared for RT-PCR and Western blotting to obsevre the semi-quantitate gene transcription and protein expressions of HIF-1α and GLUT-1. Results As compared with control group, TBI group showed increased expressions of HIF-1α and GLUT-1 4, 8 and 12 h, and 1 and 3 d after TBI （P〈0.05）; however, no significant difference was found at 1 h, 7 and 14 d after TBI （P〉0.05）. As compared with those in the TBI group and control group, the levels of HIF-1α and GLUT-1 in HPCT group began to increase at 1 hafterTBI, and markedly increased at other time points （4, 8and12h, andl, 3and7d） （P〈0.05）; however, the expressions showed no significant difference at 14 d after TBI （P〉0.05）. Conclusions HPC can improve hypoxia tolerance of brain tissues after TBI. Neuroprotection of HPC may somewhat be related to adjust the cerebral glucose metabolic pathway inducing GLUT-1 mRNA and protein expressions through up-regulating HIF-1αexpression in cerebral cortex in rats with TBI.

关 键 词：缺氧预处理 创伤性脑损伤 大脑皮层 HIF-1Α GLUT-1 

分 类 号：R651.15[医药卫生—外科学]