缺氧缺血性脑损伤新生大鼠内质网应激相关因子的表达  

Expression of Endoplasmic Reticulum Stress-Related Factor in Neonatal Rats with Hypoxic-Ischemic Brain Damage

作　　者：曹修丽[1] 王军[1] 徐艳[1] 李燕[1] 朱冠南[1] 潘红[1] 

机构地区：[1]徐州医学院附属医院新生儿科,江苏徐州221002

出　　处：《实用儿科临床杂志》2011年第20期1588-1590,共3页Journal of Applied Clinical Pediatrics

基　　金：江苏省省属高校自然科学基础研究计划项目(08KJB320019)

摘　　要：目的观察内质网应激相关因子氧调节蛋白150(ORP150)和C/EBP同源蛋白(CHOP)在缺氧缺血性脑损伤(HIBD)新生大鼠脑皮质内的表达,探讨内质网应激在新生大鼠HIBD中的作用。方法新生7日龄SD大鼠随机分为假手术组和缺氧缺血(HI)组。每组按照观测的时间点不同分为3 h、6 h、12 h、24 h、3 d、7 d 6个亚组,每个亚组8只。在每个时间点将大鼠断头后取皮质脑组织匀浆,用Western blot方法检测不同时间点其脑皮质ORP150及CHOP的动态变化。用原位末端标记法检测相应时间点光镜下其脑皮质组织的凋亡细胞数。结果 1.HI组CHOP表达水平在HIBD后各时间点均高于假手术组(P<0.05),且在24 h达到高峰;ORP150表达水平在完成HIBD后3 h开始增加,6 h达到高峰,后逐渐下降,7 d时与假手术组比较差异无统计学意义(P>0.05)。2.HI后3 h,HI组即发现结扎侧脑皮质有少量的凋亡细胞,随着HI时间的延长,凋亡细胞逐渐增多,24 h达到高峰后下降。3.CHOP的表达变化与神经细胞凋亡时间趋势呈正相关(r=0.911,P<0.05)。结论 HIBD诱发了内质网应激,可能通过上调ORP150表达参与启动未折叠蛋白反应过程,而通过上调CHOP表达诱导神经细胞凋亡的发生。Objective To detect the expression of oxygen regulate protein 150（ORP150） and C/EBP homologous protein（CHOP）,and to explore the role of endoplasmic reticulum stress playing in hypoxic-ischemic brain damage（HIBD） in neonatal rats. Methods Seven-day-old Sprague-Dawley rats were randomly assigned into 2 groups：sham operation group and hypoxic-ischemic（HI） group,then they were further divided into 6 subgroups according to the time points at 3 h,6 h,12 h,24 h,3 d and 7 d,respectively.There were 8 rats in each subgroup.Cellular proteins were extracted from cerebral cortex tissue.The expressions of ORP150 and CHOP were examined by Western blot.The apoptotic cells in cortex were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Results 1.Compared with the sham operation group,the expression level of CHOP were up-regulated in neonatal rats with HI at different time points（P0.05）,and reached the peak at 24 h after HI.However,the expression level of ORP150 began to increase at 3 h,and reached the peak at 6 h and then gradually declined.The expression of ORP150 in HI group and sham operation group had no difference at 7 d（P0.05）.2.In HI group,it was found a small number of apoptotic cells in the cerebral cortex of ipsilateral hemisphere at 3 h after HIBD.The apoptotic cells number gradually increased and reached the peak at 24 h and then decreased.3.The expression development of CHOP was positively correlated with the changes of the apoptotic cells counting after HI in neonatal rats（r=0.911,P0.05）. Conclusions HIBD may induce endoplasmic reticulum stress,which is achieved possibly through ORP150 initiating unfolded protein response reaction and CHOP up-regulation induced neuronal apoptosis.

关 键 词：内质网应激 氧调节蛋白150 C/EBP同源蛋白 缺氧缺血性脑损伤 大鼠 

分 类 号：R722.1[医药卫生—儿科]