《中国康复理论与实践》

《中国康复理论与实践》

• 专题 • 上一篇    下一篇

细胞外调节蛋白激酶信号通路对蛛网膜下腔出血大鼠神经元自噬及早期脑损伤的影响①

刘俊杰1，赵雅宁1，刘仁杰1，丁家杉1，陈禹廷1，徐继伟1，李建民2，田景瑞3   

  1. 1. 华北理工大学，河北唐山市063000；2. 华北理工大学附属医院神经外科，河北唐山市063000；3. 华北理工大学基础医学院，河北省慢性疾病重点实验室，唐山市慢性病临床基础研究重点实验室，河北唐山市063000。
  • 出版日期:2016-10-25 发布日期:2016-12-05

Effect of Extracellular Regulated Protein Kinases Signaling Pathway on Early Brain Injury and Neurons Autophagy in Rats with Subarachnoid Hemorrhage

LIU Jun- jie1, ZHAO Ya- ning1, LIU Ren- jie1, DING Jia- shan1, CHEN Yu- ting1, XU Ji- wei1, LI Jian- min2, TIAN Jing-rui3   

  1. 1. North China University of Science and Technology, Tangshan, Hebei 063000, China; 2. Department of Neurosurgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, China; 3. Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei 063000, China
  • Published:2016-10-25 Online:2016-12-05

PDF (PC)

摘要： 目的探讨细胞外调节蛋白激酶(ERK)信号通路在蛛网膜下腔出血(SAH)后早期脑损伤及海马区神经细胞自噬中的作用。方法成年雄性Sprague-Dawley 大鼠48 只，随机数字表法分为假手术组(Sham 组)、SAH组、SAH+二甲基亚砜(DMSO)组和SAH+U0126 组，每组各12 只。采用血管内穿刺法制作SAH 模型。造模前30 min，SAH+U0126 组经尾静脉注射U0126 0.05 mg/kg，Sham组和SAH组注射等体积生理盐水，SAH+DMSO组注射等体积DMSO，24 h 后处死。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，免疫组化及Western blotting 检测海马区磷酸化ERK(p-ERK)及Beclin-1 和LC3-Ⅱ表达水平。结果与Sham 组比较，SAH组脑组织含水量增加(P<0.05)，大鼠海马CA1 区神经元数量明显减少(P<0.05)，p-ERK及Beclin-1 和LC3-Ⅱ的表达升高(P<0.05)。与SAH组相比较，SAH+U0126 组脑组织含水量升高(P<0.05)，海马CA1 区神经元数量减少(P<0.05)，p-ERK及Beclin-1、LC3-Ⅱ的表达降低(P<0.05)；SAH+DMSO组各项无显著性差异(P>0.05)。结论ERK信号通路的激活可能通过对自噬的调控减轻SAH后的早期脑损伤。

关键词: 蛛网膜下腔出血, 早期脑损伤, 自噬, 细胞外调节蛋白激酶, 大鼠

Abstract: Objective To explore the effect of extracellular regulated protein kinases (ERK) signaling pathway on early brain injury and autophagy of nerve cell in hippocampus area in rats with subarachnoid hemorrhage (SAH). Methods Forty-eight adult male Sprague-Dawley rats were randomly divided into sham group, SAH group, SAH+dimethyl sulfoxide (DMSO) group and SAH+U0126 group, with 12 rats in each group. The SAH model was established with puncture of internal carotid artery. The SAH+U0126 group was injected with U0126 0.05 mg/kg; the sham group and SAH group were injected with normal saline, and the SAH+DMSO group was injected with DMSO 30 minutes before modeling. They were sacrificed 24 hours after modeling. The brain water content was measured with wet and dry method. The morphology changes of neural cells in hippocampus CA1 were observed by HE staining. The expression of phosphorylation ERK (p-ERK), Beclin-1 and LC3-Ⅱ were detected with immunohistochemical method and Western blotting. Results Compared with the sham group, the brain water content increased (P<0.05), the number of survival neurons decreased (P<0.05), the expression of p-ERK, Beclin-1 and LC3-Ⅱ increased in SAH group (P<0.05). Compared with SAH group, the brain water content increased, the number of survival neurons decreased (P<0.05), the expression of p-ERK, Beclin-1 and LC3-Ⅱ decreased in SAH+U0126 group (P<0.05); and no significant difference was found in SAH+DMSO group (P>0.05). Conclusion The activation of ERK signaling pathway may alleviate early brain injury after SAH by regulation of autophagy.

Key words: subarachniod hemorrhage, early brain injury, autophagy, extracellular regulated protein kinases, rats