GRP78、CHOP在创伤性颅脑损伤中的表达及意义  

Expression and significance of GRP78 and CHOP following TBI

作　　者：熊学华[1] 孙晓川[1] 周帅[1] 唐爽[1] 

机构地区：[1]重庆医科大学附属第一医院:神经外科,重庆400016

出　　处：《激光杂志》2013年第5期94-96,共3页Laser Journal

基　　金：国家自然科学基金面上项目(30973087);国家临床重点专科建设项目经费资助(财社120112170号)

摘　　要：目的:检测小鼠颅脑损伤后内质网应激关键标记分子葡萄糖调节蛋白78(GRP78)、C/EBP家族同源蛋白(CHOP)表达水平变化,以探讨内质网应激在创伤性颅脑损伤(TBI)中的作用。方法:选取C57BL/6J小鼠48只随机分为假手术组、TBI组,各组按伤后灌注取脑时间又分为1d、3d、7d三个亚组(n=8)。TBI组采用控制性皮质冲击颅脑损伤模型,假手术组仅行颅骨开窗。Western blot及免疫组化检测脑挫伤周围组织内质网应激标记性分子GRP78及CHOP蛋白的表达,TUNEL检测神经细胞凋亡指数,并对CHOP表达水平与细胞凋亡指数进行相关性分析。结果与假手术组相比,TBI组伤后GRP78、CHOP的表达明显上调(P<0.05),其中GRP78表达于伤后1d达到高峰,CHOP于3d后达到高峰。TBI组伤后神经细胞凋亡数量明显增加(P<0.05),于伤后3d达到高峰,相关性分析结果表明CHOP表达水平与细胞凋亡指数呈正相关(r=0.667,P<0.05)。结论:TBI后内质网应激水平上调,其介导的凋亡途径可能是导致TBI后神经细胞凋亡的重要机制之一。Objective ：To investigate the change of the expression of GRP78 and CHOP following TBI ,aim to investigate the significance of endoplasmic reticulum（ER） stress following TBI .Methods C57BL/6J mice（n=48） were randomized into sham operation group （n=24） and TBI group（n=24） .Each group was divided into 3 subgroups（n=8） according to the time of removal of the brain tissues from sacrificed animals post -TBI ：1d ,3d ,7d .The expressions of GRP78 and CHOP in the periphery of contusive and lacerated brain tissues were examined with Western blot and immunohistochemical .The TUNEL technique was used to evaluate the apoptotic rate ,while and the correlation between the level of CHOP and the apoptotic rate was analyzed .Results Compared with the sham operation group ,the expression of GRP78 and CHOP was increased in TBI group after brain injury （P〈0 .05） .The levels of GRP78 and were maximum at 1d ,While the level of CHOP was reached peak at 3d .The apoptotic rate was considerable elevated in TBI group ,and the correlation analysis showed the expression of CHOP was positive correlated with the apoptotic rate （r=0 .667 ,P〈0 .05） .Conclusion ER stress is upregulated after TBI ,which suggests that ER stress -induced apoptosis may play an important role in the pathogenesis of TBI .

关 键 词：创伤性颅脑损伤 内质网应激 凋亡 葡萄糖调节蛋白78 C EBP家族同源蛋白 

分 类 号：TN248.1[电子电信—物理电子学]