脑缺血再灌注后生长相关蛋白和勿动蛋白基因表达与神经行为功能的关系(英文)

Relationship between growth associated protein and Nogo protein gene expression after cerebral ischemia reperfusion and nervous behavioral function

背景:生长相关蛋白(GAP-43),勿动蛋白A(Nogo-A)与中枢神经损伤后的再生修复有密切关系,但其基因表达与神经行为功能的关系研究较少。目的:观察大鼠脑缺血再灌注后GAP-43和Nogo-A基因表达与神经行为功能的关系。设计:随机对照的基础实验研究。地点和对象:本实验在青岛大学医学院脑血管病研究所和山东省脑血管病防治重点实验室完成。成年健康雌性SD大鼠36只,体质量230～280g,清洁级,由中国科学院上海实验动物中心提供。干预:以线栓法建立大脑中动脉缺血再灌注模型。应用Bederson神经功能评分法评定脑缺血再灌注后神经行为功能的恢复,原位杂交技术检测脑组织GAP-43mRNA和Nogo-AmRNA的表达。主要观察指标:脑缺血再灌注后神经行为功能,脑组织GAP-43mRNA和Nogo-AmRNA的表达。结果:脑缺血再灌注后神经功能评分于再灌注2～14d降低,与缺血再灌注2h比较,差异有显著性意义。在皮质区和纹状体区,脑缺血后GAP-43mRNA表达(阳性细胞数/视野)。于再灌注12h和2d出现“双峰”升高现象,以后逐渐降低,再灌注14d,恢复至假手术组水平。No-go-AmRNA表达(阳性细胞数/视野)。也于12h和2d出现“双峰”增高,但于再灌注7d降至假手术组水平。结论:GAP-43mRNA表达增高和Nogo-AmRNA表达早期升高、晚期下降。

BACKGROUND:Growth associated protein-43(GAP-43)and Nogo protein-A(Nogo-A)have close relation to the regeneration and reparation following central nervous system injury,however, there are only a few researches on the relationship between gene expression and nervous behavioral function.OBJECTIVE:To observe the relationship between gene expressions of GAP-43 and Nogo-A after cerebral ischemic reperfusion and nervous behavioral function in rats. DESIGN:Randomized controlled basic experiment. SETTING and PARTICIPANTS:This experiment was finished in the Institute of Cerebrovascular Diseases,Medical College of Qingdao University and the Key Laboratory of Cerebrovascular Diseases of Shandong Province. Totally 36 healthy adult female Sprague-Dawley(SD)rats,weighing 230 g to 280 g, clear grade,were purchased from Shanghai Experimental Animal Center of Chinese Academy of Sciences.INTERVENTIONS:The model of focal ischemic reperfusion in SD rats was induced by intraluminal middle cerebral artery occlusion with a nylon monofilament suture.Bederson's neurological grade evaluation was used to examine the nervous behavioral function recovery,in situ hybridization was performed to examine the expression of GAP-43 mRNA and Nogo-A mRNA in the brain tissue. MAIN OUTCOME MEASURES:Nervous behavioral function,the expression of GAP-43 mRNA and Nogo-A mRNA in brain tissue after cerebral ischemic reperfusion.RESULTS:Neurological function score was decreased 2-14 days after the cerebral ischemic reperfusion,which had significant difference as compared with that 2 hours' ischemid reperfusion.In the cortex and striatum,GAP-43 mRNA(positive cells number/visual field)expressed as “double-peak' increase 12 hours and 2 days after reperfusion,and then decreased gradually to the level of the sham-operation group 14 days after reperfusion.Nogo-A mRNA expression(positive cells number/visual field)also increased as “double-peak' at 12 hours and 2 days,but reduced to the level of sham-operation group 7 days after reperfusion.CONCLUSION:Neurological function recovery after cerebral ischemic injury may be due to the upregulation of GAP-43 mRNA and the increase in the early period and decrease in the later period of Nogo-A mRNA.