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内质网应激相关CHOP在SAH后细胞凋亡中的作用及机制 被引量:1

Mechanism of apoptosis in endoplasmic reticulum stress-related CHOP after subarachnoid hemorrhage in rats
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摘要 目的探讨内质网应激(endoplasmic reticulum stress,ERS)相关C/EBP同源蛋白(C/EBP homoiogousprotein,CHOP)在蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后神经元凋亡的作用机制。方法血管内穿刺方法建立大鼠SAH模型,脑室内给药建立SAH+sh-con组和SAH+sh-RNAi组,应用神经行为学评分法进行神经行为学评分,Real-time PCR检测Caspase-3、Bim、Bcl-2的mRNA表达,Western blot检测CHOP蛋白表达,TUNEL法检测神经元凋亡。结果 SAH组和SAH+sh-con组Caspase-3、Bim mRNA及CHOP蛋白表达较空白组明显增多,Bcl-2mRNA表达减少,神经元凋亡增多(P<0.05);与空白组比较,SAH+sh-RNAi组Caspase-3、Bim mRNA及CHOP蛋白表达增多,Bcl-2mRNA表达减少,神经元凋亡增多,差异有统计学意义(P<0.05),而与SAH组和SAH+sh-con组比较,Caspase-3、Bim mRNA及CHOP蛋白表达减少,Bcl-2mRNA表达增多,神经元凋亡减少,差异具有统计学意义(P<0.05);CHOP蛋白表达增多与神经元凋亡之间存在正相关(r=0.832,P<0.05)。结论 ERS凋亡通路参与了SAH后神经元凋亡过程,抑制CHOP蛋白表达可以有效减少凋亡以改善预后。 Objective To explore the mechanism of endoplasmic reticulum stress(ERS)C/EBP homologous protein homoiogousprotein(CHOP)on neuronal apoptosis after subarachnoid hemorrhage(SAH).Methods SAH model was established by endovascular perforation technique,intraventricular administration in SAH+sh-con group and SAH+sh-RNAi group.Neurological score was used to evaluate neurological behavior of the rats.Real-time PCR and Western blot were used to detect the expressions of caspase-3,Bim,Bcl-2 mRNA and CHOP protein.Neuronal apoptosis was detected by TUNEL.Results The expressions of Caspase-3 and Bim mRNA,and CHOP protein as well as neuronal apoptosis increased significantly;Bcl-2 mRNA decreased significantly in SAH group and SAH+sh-con group(P<0.05).The expressions of Caspase-3 and Bim mRNA,and CHOP protein as well as neuronal apoptosis decreased,while Bcl-2 mRNA expression increased in SAH+sh-RNAi group compared with SAH group and SAH+sh-con group(P<0.05).There was a positive correlation between the expression of CHOP protein and neuronal apoptosis(r=0.832,P<0.05).Conclusion Endoplasmic reticulum stress-apoptosis pathway is involved in the process of neuronal apoptosis after SAH.Inhibition of CHOP protein expression can effectively reduce apoptosis and improve prognosis.
作者 郝璞珩 王辉 卫萍 金林 陈斌 HAO Pu-heng;WANG Hui;WEI Ping;JIN Lin;CHEN Bin(Department of Neurosurgery,The First Affiliated Hospital of Xi'an Medical University,Xi'an 710077;Department of Rehabilitation,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061;Xi'an Medical University,Xi'an 710021,China)
出处 《西安交通大学学报(医学版)》 CAS CSCD 北大核心 2018年第5期665-669,共5页 Journal of Xi’an Jiaotong University(Medical Sciences)
基金 陕西省教育厅科研计划项目(No.16JK1656) 西安医学院学科建设经费资助~~
关键词 蛛网膜下腔出血 早期脑损伤 内质网应激 C/EBP同源蛋白 凋亡 subarachnoid hemorrhage early brain injury endoplasmic reticulum stress C/EBP homoiogousprotein apoptosis
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