FK506对大鼠弥漫性轴索损伤后神经元凋亡及轴突再生相关蛋白表达的影响  

The influence of FK506 on the expressions of proteins related to neuronal apoptosis and regeneration following diffuse axonal injury in rats

作　　者：黄廷钦[1] 宋锦宁[1] 李宇[1] 胡明军[1] 赵雅慧[1] 刘晓斌[1] 郭小叶[1] 郑锋伟 

机构地区：[1]西安交通大学医学院第一附属医院神经外科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2015年第1期45-53,共9页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.30471774);教育部新世纪优秀人才支持计划资助项目(No.NCET-05-0831);陕西省自然科学基金资助项目(No.2003C1-16)~~

摘　　要：目的研究FK506对大鼠弥漫性轴索损伤后神经元凋亡及轴突再生相关蛋白神经丝蛋白200(NF200)、神经生长相关蛋白43(GAP-43)、凋亡相关蛋白激酶1(DAPK1)表达的影响。方法通过头颅瞬间旋转损伤装置建立大鼠弥漫性轴索损伤模型,90只SD成年雄性大鼠随机分为假手术组、DAI模型组、FK506干预组(各组又分为6h、1d、7d亚组,各组n=10);各组于预定时间点采用mNSS法评估神经功能,免疫组化染色法检测DAPK1、NF200的表达变化,Western blot法检测GAP-43的表达变化、TUNEL检测神经元凋亡,实验数据以均数±标准差记录,使用统计学SPSS 18.0软件进行单因素方差分析,以P<0.05为差异有统计学意义。结果 FK506干预组较DAI组损伤后的NF200标记轴索病理改变显示,形成轴索肿胀、轴索球数目明显降低;FK506干预组较DAI组各时间点DAPK1蛋白表达明显降低,神经元凋亡数目明显减少,GAP-43、NF200蛋白表达明显升高。结论 FK506能够在DAI后减少神经元细胞凋亡与轴索病理改变,减轻神经组织损伤;FK506能够加速神经元再生,促进脑组织损伤的修复。Objective To explore the influence of FK506 on the expressions of DAPK1, NF200 and GAP-43, proteins related to neuronal injury and regeneration following diffuse axonal injury （DAD in rats. Methods The model of DAI by instant head rotation was produced in 90 adult male SD rats. The rats were randomly divided into three groups： sham group without injury, DAI group, and FK506 intervention group. Each group was divided into 6 h, 1 d and 7 d sub-groups with 10 rats in each. The nerve function of each group was detected by the modified neurological severity scores （mNSS） at scheduled time points. The expressions of DAPKI and NF200 were detected using immunohistochemistry staining method; the expression of GAP-43 was detected using Western blot; and the number of the apoptotic neurons after DAI was counted by TUNEL staining. Data were expressed as the mean values ~ standard deviation. All data were analyzed with the Statistical Package for the Social Sciences version 18.0. A value of P^O. 05 was considered statistically significant. Results In the FK506 intervention group, the expression of DAPK1 protein was significantly reduced, and the number of apoptotic neurons decreased significantly compared with those in the DAI group at each time point. NF200 labeled axonal pathology showed that axonal swelling and axonal ball number were decreased in the FK506 intervention group compared with the DAI group. In the FK506 intervention group, the expression of DAPK1 protein and the number of apoptotic neurons were reduced significantly those in the after DAI, repair of br at each time DAI group. point; the expressions of GAP-43 and NF200 protein increased significantly compared with Conclusion thus lessening nerve tissue am t^ssue injury FK506 can reduce the apoptosis of neurons and axon pathological changes injury. FK506 can also accelerate the regeneration of neurons and promote the repair of brain tissue injury.

关 键 词：FK506 弥漫性轴索损伤 神经丝蛋白200 神经生长相关蛋白43 凋亡相关蛋白激酶1 细胞凋亡 颅脑损伤 

分 类 号：R651.15[医药卫生—外科学]