缺氧预处理对颅脑外伤大鼠海马GADD34表达及神经元细胞凋亡的影响

发布时间：2018-04-07 15:13

本文选题：颅脑外伤　切入点：缺氧预处理　出处：《安徽医科大学学报》2017年01期

【摘要】：目的探讨缺氧预处理对颅脑外伤大鼠海马生长停滞与DNA损害可诱导基因34(GADD34)表达及神经元细胞凋亡的影响。方法 208只SD雄性大鼠,随机分为假手术(Con,n=8)组、缺氧预处理(HPC,n=8)组、颅脑外伤(TBI,n=96)组、缺氧预处理颅脑外伤(HPCT,n=96)组;TBI和HPCT组再根据不同处死时间分为1 h、3 h、6 h、12 h、24 h、3d、7 d、14 d八个亚组。大鼠颅脑外伤模型采用改良的自由落体装置制作,预先将大鼠在低压氧仓(-50.47 k Pa)内处理3 h/d,连续3 d制作缺氧预处理模型。采用改良Sugrwara法对大鼠伤后行为学评估;RT-PCR和Western blot法检测海马组织中GADD34的表达变化,TUNEL染色法检测凋亡神经元细胞。结果海马中GADD34 mRNA和蛋白伤后1 h即有表达,3~12 h呈上升趋势,伤后24 h达高峰,3~14 d呈下降趋势,TBI与Con组,HPCT与HPC组比较,差异均有统计学意义(P0.05);伤后24 h各指标进行比较,Con和HPC组比较,差异无统计学意义,其中HPCT组中伤后行为学评估得分及GADD34的表达较TBI组显著增高,细胞凋亡率显著降低,差异均有统计学意义(P0.05)。结论缺氧预处理可降低颅脑外伤大鼠海马行为学损伤,其机制可能是通过上调海马GADD34的表达,降低海马神经元细胞凋亡,从而发挥脑保护作用。
[Abstract]:Objective to investigate the effects of hypoxia preconditioning on the expression of 34 GADD34 gene and neuronal apoptosis in hippocampus of rats with craniocerebral injury.The rat model of craniocerebral trauma was made with an improved free-fall device. The model of hypoxia preconditioning was established by pretreating the rats in a hypobaric oxygen chamber (-50.47kPa) for 3 h / d for 3 days.The changes of GADD34 expression in hippocampal tissue were detected by modified Sugrwara method and Western blot method. Tunel staining was used to detect apoptotic neurons.Results the expression of GADD34 mRNA and protein in hippocampus increased at 12 h after injury, and decreased at 24 h after injury. The expression of HPCT in TBI group was significantly higher than that in Con group (P < 0 05), and the expression of HPCT in Con group was higher than that in HPC group (P < 0 05).There was no significant difference between Con group and HPC group at 24 hours after injury. The scores of behavioral evaluation and GADD34 expression in HPCT group were significantly higher than those in TBI group, and the apoptosis rate was significantly lower than that in TBI group.The difference was statistically significant (P 0.05).Conclusion hypoxic preconditioning can reduce the behavioral injury of hippocampus in rats with craniocerebral trauma. The mechanism may be that by up-regulating the expression of GADD34 in hippocampus and decreasing the apoptosis of hippocampal neurons, hypoxia preconditioning may play a protective role in the brain.
【作者单位】：安徽医科大学解放军临床学院(解放军第105医院)神经外科;
【基金】：全军医学科学技术研究“十二五”科研项目(面上)(编号:CWS11J262) 南京军区医学科技创新重点课题(编号:09Z009)
【分类号】：R651.15

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