促红细胞生成素对外伤性颅脑损伤大鼠神经丝的保护作用  

Neuroprotective effect of EPO on neurofilaments in rats with traumatic brain injury

作　　者：刘健[1] 高佳星[2] 汪叶松[3] 

机构地区：[1]四川省绵阳市人民医院脑外科,四川绵阳621000 [2]四川省绵阳市人民医院妇产科,四川绵阳621000 [3]浙江大学医学院附属第二医院脑外科,浙江杭州310000

出　　处：《中国生化药物杂志》2015年第2期63-65,70,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：2012年浙江省医药卫生科技计划(2012KYB096)

摘　　要：目的 观察促红细胞生成素（erythropoietin EPO）对创伤性颅脑损伤（traumatic brain injury,TBI）大鼠脑皮质中神经丝的影响,并探讨其意义.方法 45只Wistar大鼠按随机原则分为9组,正常对照组、颅脑损伤组（各组于建模后6、12、24、72 h取标本）,EPO处理组（各组于建模后6、12、24、72 h取标本）,每组5只,采用Myneurolab脑立体定向仪和Benchmark颅脑损伤撞击器制作创伤性颅脑损伤模型.应用免疫组化法观察上述时间点损伤灶周围皮层神经丝的形态改变,Western blot检测各时间点中神经丝蛋白H（neurofilament H,NF-H）的表达变化.结果 免疫组化结果显示：正常对照组NF-H含量丰富,呈棕黄色丝状结构,在脑皮质的大椎体细胞层、小椎体细胞层,海马区,胼胝体中表达尤为明显,而颅脑损伤组于脑外伤后6h见NF-H较正常组稀疏,部分结构中断,6～24h内可见神经丝数目进一步减少,排列紊乱加重,至24h破坏程度达到高峰,72 h时上述情况有所缓解,外伤后EPO处理组神经丝数量在各个时间点均比外伤组多,且排列较外伤组整齐.神经丝的密集程度在12h达到高峰,然后逐渐降低.Western blot显示：与正常组相比,颅脑损伤组损伤后6h可见NF-H的表达减少（P＜0.05）.6～12h内NF-H蛋白表达持续减少（P＜0.05）,24h后达最低值（P＜0.01）,72 h时升高（P＜0.05）.但与颅脑损伤各组比较,EPO处理组NF-H的表达升高（P＜0.05）.结论 EPO对脑具有保护作用,其可能机制为抑制神经丝蛋白降解.Objective To observe the erythropoietin（ EPO） on neurofilaments in rats traumatic brain injury（ TBI） and its significance.Methods 45 Wistar rats were divided into nine groups： normal control group,brain injury（ 6,12,24,72 h after brain injury）,and EPO treatment after brain injury（ 6,12,24,72 h after brain injury）. The Myneurolab of stereotactic apparatus and the Benchmark of traumatic brain injury impactor were used to produce TBI model. The morphologic changes of neurofilament were observed by immunohistochemistry in lesion peri cortex,and the expressions of neurofilament H（ NF-H） were detected by Western blot at the above time points. Results The immunohistochemistry result showed that in normal control group,NF-H was abundant in tissue section with the tan filamentous structure,and existed in big cones,small cones,hippocampus,especially obvious in corpus callosum of cerebral cortex layer; in brain injury group,NF-H was sparse with part of the structure interrupted after traumatic brain injury of 6h,further nerve filament number reduced with disordered arrangement after 6 ~ 24 h,the damage reached its peak after 24 h,and the above situation eased after 72 h. The number of neurofilaments in EPO treatment group at each time point was higher than that in brain injury group after trauma,arranged neatly and the intensity of neurofilament reached the peak at 12 h,then gradually reduced. Western blot result showed that compared with normal group,the expression of NF-H reduced after traumatic brain injury of 6h（ P〈 0. 05）,within 6 ~ 12 h NF-H protein expression persistent decrease（ P〈 0. 05）,reached the lowest after 24 h（ P〈 0. 01）,and elevated after 72 h（ P〈 0. 05）. But compared with groups of brain injury,the expression of NF- H decreased in EPO treatment group（ P〈 0. 05）. Conclusion EPO has a neuroprotective effect,and its possible mechanism is to inhibit the degradation of neurofilament protein.

关 键 词：促红细胞生成素 创伤性脑损伤 神经丝 

分 类 号：R3[医药卫生—基础医学]