ERK信号通路抑制剂U0126对蛛网膜下腔出血大鼠早期脑损伤及神经元自噬的影响

摘要:目的探讨ERK信号通路特异性抑制剂U0126对蛛网膜下腔出血(SAH)对早期脑损伤及海马区神经细胞自噬的作用。方法成年雄性SD大鼠48只,随机数字表法分为对照组、SAH组、DMSO+SAH(二甲基亚砜)组、U0126+SAH组(ERK信号通路特异性抑制剂),共4组,每组各12只。采用血管内穿刺法(PIC)法制作SAH模型,分别于造模前30min经尾静脉注射等量的生理盐水、DMSO、U0126溶液0.5mL/只,于24h处死。干湿重法测量脑组织水含量,HE染色观察海马CA1区神经细胞形态结构变化;免疫组化及Westernbloting检测海马区ERK及Beclin-1和LC3-Ⅱ表达水平的...

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Published in西安交通大学学报(医学版) Vol. 38; no. 1; pp. 18 - 23
Main Author 刘俊杰 赵雅宁 陈禹廷 付程凯 丁家杉 徐继伟 李建民
Format Journal Article
LanguageChinese
Published 华北理工大学 附属医院神经外科,河北唐山,063000%华北理工大学 护理与康复学院,河北唐山,063000 2017
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ISSN1671-8259
DOI10.7652/jdyxb201701004

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Summary:摘要:目的探讨ERK信号通路特异性抑制剂U0126对蛛网膜下腔出血(SAH)对早期脑损伤及海马区神经细胞自噬的作用。方法成年雄性SD大鼠48只,随机数字表法分为对照组、SAH组、DMSO+SAH(二甲基亚砜)组、U0126+SAH组(ERK信号通路特异性抑制剂),共4组,每组各12只。采用血管内穿刺法(PIC)法制作SAH模型,分别于造模前30min经尾静脉注射等量的生理盐水、DMSO、U0126溶液0.5mL/只,于24h处死。干湿重法测量脑组织水含量,HE染色观察海马CA1区神经细胞形态结构变化;免疫组化及Westernbloting检测海马区ERK及Beclin-1和LC3-Ⅱ表达水平的变化。结果与Sham组比较,SAH模型组脑组织含水量明显增加,大鼠海马CA1区神经元数量明显减少(P〈0.05),ERK及自噬相关因子Beclin-1和LC3-Ⅱ的表达明显高于对照组(P〈0.05);与SAH模型组比较,U0126组脑组织含水量明显增多,海马CA1区神经元数量明显较SAH组减少(P〈0.05),ERK信号信号通路被抑制,相应自噬相关因子Beclin-1和LC3-Ⅱ的表达降低(P〈o.05)。结论ERK信号通路抑制剂U0126可以抑制神经细胞自噬,加重SAH的早期脑损伤。
Bibliography:LIU Jun-jie , ZHAO Ya-ning , CHEN Yu-ting , FU Cheng-kai , DING Jia-shan , XU Ji-wei , LI Jian-min (1. Department of Neurosurgery, the Affiliated Hospital of North China University of Science and Technology, Tangshan 063000; 2. Department of Nursing and Rehabilitation, North China University of Science and Technology, Tangshan 063000, China)
subarachniod hemorrhage; early brain injury; autophagy; extracellular regulated protein kinase(ERK)
Objective To explore role of U0126, the specific inhibitor of ERK signaling pathway, in early brain injury (EBI) and the autophagy of nerve cells in hippocampus area in subarachnoid hemorrhage (SAH). Methods A total of 48 male adult SD rats were randomly divided into control group, SAH group, DMSO-FSAH group, and U0126-FSAH group, with 12 in each. We established SAH rat model by the puncture of internal carotid artery. The same amount of saline water, DMSO and U0126 solution of 0.5 mL per rat was injected respectively into the rats of different groups 30 min before modeling.
ISSN:1671-8259
DOI:10.7652/jdyxb201701004