缺氧预处理对创伤性脑损伤大鼠SphK-1表达及血脑屏障通透性的影响  

Effect of hypoxic preconditioning on sphingosine kinase-1 expression and blood-brain barrier permeability in rats after traumatic brain injury

作　　者：姚寅生 刘家传[1] 杨艳艳[1] 张星[1] 黄振山[1] 温玉东 

机构地区：[1]中国人民解放军第一〇五医院神经外科,合肥230031

出　　处：《中华神经医学杂志》2014年第7期672-676,共5页Chinese Journal of Neuromedicine

基　　金：全军医学科技“十二五”科研项目（CWS11J262）;2009年度南京军区医学科技创新重点课题（092009）

摘　　要：目的探讨缺氧预处理（HPC）对创伤性脑损伤（TBI）大鼠脑组织鞘氨醇激酶-1（SphKl）表达及血脑屏障fBBB）通透性的影响。方法204只sD大鼠采用随机数字表法分TBI组（96只）、HPC组（96只）和空白对照组（CON组）（12只），其中前2组分伤后1h、4h、8h、12h、1d、3d、7d、14d8个亚组，每亚组12只。HPC组大鼠行HPC预处理3d（-50kPa、3h／d）后采用Feeney自由落体打击法建立TBI模型，TBI组仅建立TBI模型。各组大鼠于相应时间点处死后RT-PCR和Western blotting检测挫伤区周围脑组织SphK-1mRNA和蛋白的表达，免疫组化染色IgG并评分观察BBB通透性的变化。结果TBI组和HPC组大鼠脑组织IgG评分、SphK-1mRNA和蛋白的表达在TBI后1h即开始升高，1d升至最高点（SphK-1蛋白表达分别为0．694±0．016、0．854±0．010），伤后14d时仍高于CON组水平；与TBI组比较，伤后各个时间点HPC组大鼠脑组织IgG评分均较低，伤后1h、4h、8h、12h、1d、3d、7d挫伤区周围脑组织SphK-1mRNA和蛋白的表达较高，差异有统计学意义（P〈0．05）。结论HPC可以上调TBI大鼠脑组织SphK-1的表达，促进鞘氨醇（Sph）向1-磷酸鞘氨醇（S1P）转化，保护BBB完整性。Objective To explore the effect ofhypoxic preconditioning （HPC） on the expression of sphingosine kinase-1 （SphK-1） and blood-brain barrier （BBB） permeability in rats after traumatic brain injury （TBI）. Methods Two hundred and four SD rats were randomly assigned into TBI group （n=96）, HPC group （giving HPC and TBI, n=96） and blank control group （n=12）. The rats in the TBI group were subjected to TBI with freefall impact method, while the rats of HPC group were treated with the same methods after HPC （50.47 kpa, 3 d, 3 h/d）. And then, they were sacrificed at each time point （1, 4, 8 and 12 h, and 1, 3, 7 and 14 d after injury）. RT-PCR and Western blotting were employed to detect the mRNA and protein expression changes of SphK-1 in brain contusion area at each time points after injury. lmmumohistochemical staining （IgG method） was used to detect the BBB permeability changes of the rats. Results IgG scores and Sphk-1 mRNA and protein expressions in rats of TBI group and HPC group began to increase at 1 h after injury and reached the highest level 1 d after injury; they were still higher than the normal levels, with significant differences （P〈0.05）; SphK-1 mRNA and protein expressions in all the three groups had the same increased trend at all the time points excepted on the 14~ d of injury, with significant differences （/9〈0.05）. IgG scores showed that the BBB permeability in the TBI group at each time point was significantly higher than that in the HPC group （P〈0.05）. Conclusion Hypoxic preconditioning can increase SphK-1 expressions after TBI to promote sphingosine 1-phosphate sphingosine transformation so as to protect of the integrity of BBB.

关 键 词：缺氧预处理 颅脑损伤 血脑屏障 鞘氨醇激酶-1 

分 类 号：R651.15[医药卫生—外科学]