[1]黎新慎,彭建华,庞金伟,等.载脂蛋白E拟肽COG1410对蛛网膜下腔出血后自噬和凋亡的影响[J].陆军军医大学学报(原第三军医大学学报),2017,39(24):2366-2373.
 LI Xinshen,PENG Jianhua,PANG Jinwei,et al.Effects of apolipoprotein E mimetic peptide COG1410 on central autophagy and apoptosis after subarachnoid hemorrhage in mice[J].J Amry Med Univ (J Third Mil Med Univ),2017,39(24):2366-2373.
点击复制

载脂蛋白E拟肽COG1410对蛛网膜下腔出血后自噬和凋亡的影响(/HTML )
分享到:

陆军军医大学学报(原第三军医大学学报)[ISSN:1000-5404/CN:51-1095/R]

卷:
39卷
期数:
2017年第24期
页码:
2366-2373
栏目:
基础医学
出版日期:
2017-12-30

文章信息/Info

Title:
Effects of apolipoprotein E mimetic peptide COG1410 on central autophagy and apoptosis after subarachnoid hemorrhage in mice
作者:
黎新慎彭建华庞金伟李勇周牮古龙吴越黄学平孙晓川陈礼刚江涌
西南医科大学附属医院神经外科;重庆医科大学附属第一医院神经外科;泸州市人民医院神经外科
Author(s):
LI Xinshen PENG Jianhua PANG Jinwei LI Yong ZHOU Jian GU Long WU Yue HUANG Xueping SUN Xiaochuan CHEN Ligang JIANG Yong

Department of Neurosurgery,the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000; 2Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016; 3Department of Neurosurgery, Luzhou People’s Hospital, Luzhou, Sichuan Province, 646000, China

关键词:
蛛网膜下腔出血早期脑损伤自噬凋亡COG1410
Keywords:
subarachnoid hemorrhage early brain injury autophagy apoptosis COG1410
分类号:
R341;R394.1;R734.35
文献标志码:
A
摘要:

目的      研究新一代载脂蛋白(apolipoprotein E,apoE)拟肽COG1410的应用对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期脑损伤(early brain injury,EBI)期间大脑自噬及凋亡的影响。方法      选用颈内动脉穿刺法建立小鼠SAH模型,首先观察EBI期间伤侧大脑半球自噬、凋亡及相关信号蛋白的表达变化,然后针对自噬水平最活跃的时间点进行COG1410给药,采取Garcia评分评价SAH及给药后小鼠的神经功能变化,利用Western blot测定自噬、凋亡及相关信号分子蛋白的表达量,并使用免疫荧光染色观察皮层神经元的凋亡变化情况。结果     ①在SAH后EBI期间,与Sham组相比,伤侧大脑半球的自噬水平在SAH后6 h开始增加(P<0.05),并在24 h达到高峰(P<0.01),随后逐渐下降,信号分子p-GSK-3β水平也有类似的变化趋势;给予小鼠COG1410后,SAH后24 h的大脑自噬活动被进一步增强(P<0.05)。②在SAH后的EBI期间,伤侧大脑半球整体凋亡水平变化并不完全和自噬及p-GSK-3β水平变化同步,其在EBI后期仍保持相对高值,但有减弱的趋势;给予COG1410后,伤侧大脑半球和皮层神经元凋亡水平均被下调(P<0.05)。③与Sham组(16.50±1.05)比较,SAH组的Garcia评分(11.17±1.83)明显降低(P<0.01),COG1410的干预能显著改善SAH组的Garcia评分(15.17±0.75)(P<0.01),但COG1410的干预对SAH分级影响并不大。结论     COG1410的应用可能通过磷酸化GSK-3β增强SAH后EBI期间大脑的自噬活动,减弱神经元的凋亡活动,并改善模型小鼠的神经功能。

Abstract:

Objective     To determine the effect of a novel apolipoprotein E (apoE) mimetic peptide, COG1410, on the autophagy and apoptosis in early brain injury (EBI) after subarachnoid hemorrhage(SAH). Methods    Murine model of SAH was established by endovascular perforation in the carotid artery. The changes of autophagy, apoptosis and related signal protein levels in the injured hemisphere were observed.Then, COG1410 was administrated at the time point of relatively strongest autophagy.Neurological function was quantified by Garcia score in the SAH mice before and after COG1410 treatment. The expression levels of autophagy, apoptosis and the related signal protein levels were detected by Western blotting, and the apoptosis of cortical neurons were observed by immunofluorescence staining. Results    ①Compared with the sham group, the autophagy in the injured cerebral hemisphere was increased at 6 h after SAH (P<0.05), peaked at 24 h (P<0.01), and then decreased gradually.The change of p-GSK-3β was in a same trend. Administration of COG1410 at 24 h after SAH resulted in further enhanced autophagy (P<0.05). ② In the phase of EBI after SAH, the apoptosis status in the injured hemisphere was not completely synchronized with the changes of autophagy and p-GSK-3β level; The apoptosis remained at a relatively high status, though in a trend of decreasing. COG1410 treatment inhibited the apoptosis in the injured hemisphere and the apoptosis of the cortical neurons (P<0.05).③The neurological score was significantly lower in the model group than the sham group (11.17±1.83 vs 16.50±1.05, P<0.01), but the score was notably improved after the administration of COG1410 (15.17±0.75, P<0.01).But, the administration showed no obvious effect on the SAH grade. Conclusion     The administration of COG1410 may promote the brain autophagy but depress the neuronal apoptosis,and improve the neurological function by phosphorylation of GSK-3β in mice in EBI after SAH.

相似文献/References:

[1]张桓,朱继.液态氟碳纳米粒对大鼠蛛网膜下腔出血后早期脑损伤的保护作用[J].陆军军医大学学报(原第三军医大学学报),2015,37(18):1842.
 Zhang Huan,Zhu Ji.Perfluorooctyl-bromide nanoparticles protect early brain injury in rats after sub-arachnoid hemorrhage[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(24):1842.
[2]廖忆思,黄加尚,谢延风,等.蛛网膜下腔出血后早期脑损伤中ROS和PDGFR活化的研究[J].陆军军医大学学报(原第三军医大学学报),2022,44(12):1243.
 LIAO Yisi,HUANG Jiashang,XIE Yanfeng,et al.Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage[J].J Amry Med Univ (J Third Mil Med Univ),2022,44(24):1243.
[3]陈佳琳,姚声涛,郭宗铎.TNF-α在实验性蛛网膜下腔出血后早期脑损伤中的作用[J].陆军军医大学学报(原第三军医大学学报),2011,33(15):1620.
 Chen Jialin,Yao Shengtao,Guo Zongduo.Role of TNF-α in early brain injury after subarachnoid hemorrhage in rats[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(24):1620.
[4]雷波,谢宗义,马颖,等.大鼠蛛网膜下腔出血后皮质中VDAC1的表达与神经元凋亡的关系[J].陆军军医大学学报(原第三军医大学学报),2011,33(16):1705.
 Lei Bo,Xie Zongyi,Ma Ying,et al.Correlation between VDAC1 expression and neuronal apoptosis in cerebral cortex of rats in early brain injury after subarachnoid hemorrhage[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(24):1705.
[5]陈佳琳,姚声涛,陈良勇,等.米诺环素对大鼠蛛网膜下腔出血后早期脑损伤的保护作用[J].陆军军医大学学报(原第三军医大学学报),2010,32(17):1847.
 Chen Jialin,Yao Shengtao,Chen Liangyong,et al.Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(24):1847.
[6]林斌,孙晓川,张晓冬,等.APOE基因多态性与动脉瘤性蛛网膜下腔出血后早期脑功能改变的相关性[J].陆军军医大学学报(原第三军医大学学报),2010,32(07):700.
 Lin Bin,Sun Xiaochuan,Zhang Xiaodong,et al.Association between APOE polymorphism and brain function in early stage of aneurysmal subarachnoid hemorrhage[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(24):700.
[7]郭宗铎,孙晓川,何朝晖,等.蛛网膜下腔出血后早期海马MMP-9的表达与海马神经元凋亡的相关性研究[J].陆军军医大学学报(原第三军医大学学报),2009,31(01):71.
 GUO Zong-duo,SUN Xiao-chuan,HE Zhao-hui,et al.Association between hippocampal MMP-9 expression and neuronal apoptosis in early brain injury in rats after subarachnoid hemorrhage[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(24):71.
[8]许伟,朱继.液态氟碳纳米粒在大鼠蛛网膜下腔出血中对低氧诱导因子1α的抑制作用[J].陆军军医大学学报(原第三军医大学学报),2016,38(03):251.
 Xu Wei,Zhu Ji.Perfluorooctyl-bromide nanoparticles inhibit hypoxia-inducible factor 1α in early brain injury of rats after subarachnoid hemorrhage[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(24):251.
[9]张光伟,贺学农,周昌龙,等.血小板源性生长因子受体在实验性蛛网膜下腔出血后早期脑损伤中的作用[J].陆军军医大学学报(原第三军医大学学报),2013,35(13):1398.
 Zhang Guangwei,He Xuenong,Zhou Changlong,et al.Role of platelet-derived growth factor receptor in early brain injury following subarachnoid hemorrhage[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(24):1398.
[10]张红霞,蒋登志,车旭东,等.依布硒林减轻DMT1诱导的铁死亡在实验性大鼠蛛网膜下腔出血中的研究[J].陆军军医大学学报(原第三军医大学学报),2017,39(16):1618.
 ZHANG Hongxia,JIANG Dengzhi,CHE Xudong,et al.Ebselen relieves ferroptosis induced by divalent mental transporter 1 in rats with subarachnoid hemorrhage[J].J Amry Med Univ (J Third Mil Med Univ),2017,39(24):1618.

更新日期/Last Update: 2017-12-25