中国医科大学学报

中国医科大学学报
  • 中文核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
  • BA、CA收录

中国医科大学学报 ›› 2017, Vol. 46 ›› Issue (11): 995-1000.doi: 10.12007/j.issn.0258‐4646.2017.11.008

• 论著 • 上一篇    下一篇

ERK1/2和PI3-K通路抑制剂对蛛网膜下腔出血大鼠海马区 神经细胞自噬的协同作用

安朝旺1,刘瑶2,赵晓云2,韩颖2,赵雅宁2,赵旭1,李建民1,薛承景1   

  1. 华北理工大学 1 附属医院神经外科;2 护理与康复学院临床教研室,河北 唐山 063000
  • 收稿日期:2016-11-22 出版日期:2017-11-30 发布日期:2017-11-01
  • 通讯作者: 李建民 E-mail:18531776202@163.com
  • 作者简介:安朝旺(1980-),男,主治医师,硕士
  • 基金资助:
    河北省省级重大医学科研课题(zd2013087);唐山市科技 计划(14130220B)

Synergistic Effects of ERK1/2 and PI3-K Pathway Inhibitors on Autophagy in the Hippocampus of Rats with Subarachnoid Hemorrhage

AN Chaowang1,LIU Yao2,ZHAO Xiaoyun2,HAN Ying2,ZHAO Yaning2,ZHAO Xu1,LI Jianmin1,XUE Chengjing1   

  1. 1 Neurosurgery Department,Affiliated Hospital of North China University of Science and Technology,Tangshan 063000,China;2 Clinical Department,College of Nursing and Rehabilitation,North China University of Science and Technology,Tangshan 063000,China
  • Received:2016-11-22 Online:2017-11-30 Published:2017-11-01

摘要: 目的 通过观察联合抑制细胞外信号调节激酶(ERK1/2)和磷脂酰肌醇3激酶(PI3-K)蛋白对神经细胞自噬的影响,探讨蛛网膜下腔出血(SAH)救治靶点。方法 将200只雄性SD大鼠按照数字表法随机分为假手术(Sham)组、模型(SAH)组、ERK1/2 抑制剂U0126组、PI3-K抑制剂LY294002组、U0126+LY294002组。二次注血法制作SAH大鼠模型;HE染色观察海马区神经细胞的 形态变化;实时荧光定量PCR法检测ERK1/2、PI3-K、自噬相关蛋白beclin-1和微管相关蛋白1轻链(LC3)mRNA的表达,免疫组化 法检测海马区磷酸化ERK1/2、PI3-K、beclin-1和LC3-Ⅱ蛋白的表达水平。结果 SAH组海马区神经细胞死亡率、ERK1/2、PI3-K、 beclin-1和LC3 mRNA以及磷酸化ERK1/2 、PI3-K、beclin-1和LC3-Ⅱ蛋白水平均高于Sham组(均P < 0.05);U0126组和LY294002组 海马区神经细胞死亡率高于SAH组,而ERK1/2、PI3-K、beclin-1和LC3 mRNA以及磷酸化ERK1/2、PI3-K、beclin-1和LC3-Ⅱ蛋白水 平均低于SAH组(均P < 0.05);U0126+ LY294002组海马区神经细胞死亡率高于U0126或 LY294002组,而ERK1/2、PI3-K、eclin-1 和LC3 mRNA以及磷酸化ERK1/2 、PI3-K、beclin-1和LC3-Ⅱ蛋白水平分别低于U0126和 LY294002组(均P < 0.05)。结论 联合抑 制ERK1/2和PI3-K通路激活可显著降低SAH后神经细胞自噬,加重神经细胞丢失。

关键词: 蛛网膜下腔出血, 细胞外信号调节激酶, 磷脂酰肌醇3激酶, 自噬相关蛋白, 微管相关蛋白1轻链

Abstract: Objective To investigate synergistic effects of extracellular signal regulated kinase(ERK1/2)and phosphatidylinositol 3 kinase(PI3-K)pathway inhibitors on autophagy in the hippocampus of rats with subarachnoid hemorrhage(SAH),for identification of therapeutic targets in SAH. Methods Totally,200 male SD rats were randomly divided into a sham operated group,SAH group,inhibitor U0126 group,inhibitor LY294002 group,and a U0126+ LY294002 group. Animal models were established by injecting autologous blood twice into the cisterna magna. Morphological changes in the hippocampus nerve cells were detected by HE staining;ERK1/2,PI3-K,bec- lin-1,and LC3 mRNA expression in the hippocampus were detected by real-time PCR,and phosphorylated ERK1/2,PI3-K,beclin-1,and LC3-Ⅱ protein expression were detected by immunohistochemistry. Results Neuronal death rate and phosphorylated ERK1/2,PI3-K, beclin-1,and LC3-Ⅱlevels in the hippocampus in the SAH group were higher than in the sham group(all P < 0.05). Neuronal death rate in U0126 or LY294002 group was higher than in SAH group,while ERK1/2,PI3-K,beclin-1,and LC3 mRNA and phosphorylated ERK1/2, PI3-K,beclin-1,and LC3-Ⅱprotein levels were lower than in SAH group(all P < 0.05). Neuronal death rate in U0126 +LY294002 group was higher than in U0126 or LY294002 group,while ERK1/2,PI3-K,beclin-1,LC3 mRNA and phosphorylated ERK1/2,PI3-K,beclin-1, and LC3-Ⅱprotein levels in the hippocampus were lower than in U0126 or LY294002 group(all P < 0.05). Conclusion Co-targeting the inhibition of ERK1/2 and PI3-K pathways can significantly reduce neuronal cell autophagy and aggravate cells loss after SAH.

Key words: subarachnoid hemorrhage, extracellular signal regulated kinase, phosphatidylinositol 3 kinase, autophagy

中图分类号: 

  • R651.1
[1] 刘仁杰, 刘俊杰, 张尧, 王婧瑶, 王一超, 张婧曦, 梁文吉, 赵雅宁, 李建民. 亚低温通过调控内质网应激激活自噬改善蛛网膜下腔出血大鼠早期脑损伤[J]. 中国医科大学学报, 2018, 47(9): 824-828,833.
[2] 杨莹, 李肖肖, 官彦雷. 头部亚低温护理对蛛网膜下腔出血术后的影响[J]. 中国医科大学学报, 2018, 47(1): 88-90.
[3] 王翀,吴鹏飞,王明昊,刘济源. 细胞外信号调节激酶对神经胶质瘤环氧合酶2基因表达的影响[J]. 中国医科大学学报, 2014, 43(4): 333-336.
[4] 周万,周向东,尤列?皮尔曼,维克多?科罗索夫. OGR1籍ERK信号通路参与酸性微环境致气道上皮细胞黏蛋白5AC表达[J]. 中国医科大学学报, 2014, 43(2): 122-126.
[5] 王海波,朱春莹,包义君,陈书达,郭宗泽,仇波. 细胞外信号调节激酶1/2抑制剂U0126上调脑缺血再灌注小鼠海马微管结合蛋白2的表达[J]. 中国医科大学学报, 2014, 43(12): 1092-1096.
[6] 刘亚莉,易佳丽,王莹,井欢,刘春英. 补中益气汤含药血清对A549/DDP细胞PI3K/AKT信号转导通路影响的实验研究[J]. 中国医科大学学报, 2014, 43(1): 14-18.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!

中国医科大学学报版权所有©2018

未经允许,严禁擅自转载本站图文资料

地址:中国 沈阳市沈北新区蒲河路77号 110122

辽ICP备05014850

JOURNAL OF CHINA MEDICAL UNIVERSITY

ADDRESS: NO.77 PUHE ROAD

SHENYANG NORTH NEW AREA, SHENYANG

LIAONING PROVINCE, P.R. CHINA