蛛网膜下腔出血后GRP78和CHOP的表达与大鼠海马区神经元凋亡的关系

Relationship between GRP78 and CHOP expression and neuronal apoptosis in rat hippocampal region after subarachnoid hemorrhage

目的 探讨内质网应激标志性因子GRP78、CHOP的表达与蛛网膜下腔出血（SAH）后神经元凋亡的关系.方法 108只雄性SD大鼠随机分为对照组、假手术组与手术组.第1、6、12、24、48和72 h用神经功能缺陷评分法对大鼠神经行为学评分,TUNEL法检测神经元凋亡,Western blot检测GRP78和CHOP蛋白表达.结果 神经行为学评分显示,第12、24、48和72 h手术组比对照组及假手术组均明显降低,差异有统计学意义（P＜0.05）;神经元凋亡结果显示,手术组比对照组、假手术组明显增多,差异有统计学意义（P＜0.01）,手术组1h凋亡细胞较少,6h增多,24 h达到峰值,不同时间点凋亡细胞数比较差异有统计学意义（P＜0.01）;GRP78蛋白表达显示,第1、6、12、24和48 h手术组比对照组、假手术组均明显升高,差异有统计学意义（P＜0.01）,手术组1h开始上升,12h达到峰值,不同时间点比较差异有统计学意义（P＜0.01）;CHOP蛋白表达显示,手术组比对照组、假手术组明显增多,差异有统计学意义（P＜0.05）,手术组1h上升,24 h达到峰值,不同时间点比较差异有统计学意义（P＜0.01）;GRP78、CHOP与神经元凋亡之间均存在正相关（r=0.723、r=0.909,P＜0.01）.结论 GRP78和CHOP在SAH后早期脑损伤的病理过程中发挥了重要作用.

Objective To investigate the relationship between the endoplasmic reticulum stress markers GRP78,CHOP expression and the neuronal apoptosis after subarachnoid hemorrhage （SAH）.Methods A total of 108 male SD rats were randomly divided into a control group,a sham operation group,and an operation group.Neurological deficit score was used to score the neuroethology in rats at 1,6,12,24,48,and 72 h.TUNEL assay was used to detect neuronal apoptosis.Western blot was used to detect the GRP78 and CHOP protein expression.Results The neuroethology scores showed that the score of the operation group decreased significantly compared with the control and sham operation groups at 12,24,48,and 72 h.There were significant significances （P 〈 0.05）.The results of neuronal apoptosis showed that the operation group increased significantly compared with the control and sham operation groups.There were significant differences （P〈0.01）.The number of apoptotic cells was less at 1 h;it increased at 6 h and reached the peak value at 24 h.There were significant differences in comparison the number of apoptotic cells at different time points （P 〈 0.01）.The GRP78 protein expression showed that the operation group increased significantly compared with the control and sham operation groups at 1,6,12,24,and 48 h.There were significant significances （P 〈 0.01）.The level in the operation group began to increase at 1 h.There were significant differences in comparison of different time points （P 〈 0.01）.The CHOP protein expression showed that the operation group increased significantly compared with the control and sham operation groups.There were significant significances （P 〈 0.05）.The level in the operation group increased at 1 h,and it reached the peak value at 24 h.There were significant differences in comparison of the different time points （P 〈 0.01）.There was a positive correlation between GRP78,CHOP and neuronal apoptosis （r =0.723,r =0.909,P 〈0.01）.Conclusion GRP78 and CHOP play an important role in the pathological process of early brain injury after SAH.