Effects of apolipoprotein E mimetic peptide COG1410 on central autophagy and apoptosis after subarachnoid hemorrhage in mice

Xinshen LI; Jianhua PENG; Jinwei PANG; Yong LI; Jian ZHOU; Long GU; Yue WU; Xueping HUANG; Xiaochuan SUN; Ligang CHEN; Yong JIANG

doi:10.16016/j.1000-5404.201708137

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Effects of apolipoprotein E mimetic peptide COG1410 on central autophagy and apoptosis after subarachnoid hemorrhage in mice

Basic Medicine | 更新时间：2026-01-09

- Effects of apolipoprotein E mimetic peptide COG1410 on central autophagy and apoptosis after subarachnoid hemorrhage in mice
- Journal of Third Military Medical University Vol. 39, Issue 24, Pages: 2366-2373(2017)
- 作者机构：
  
  1.646000 四川泸州，西南医科大学附属医院神经外科
  2.400016 重庆，重庆医科大学附属第一医院神经外科
  3.646000 四川泸州，泸州市人民医院神经外科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81371319);the Joint Project of Luzhou Municipal Government-Southwest Medical University(2016LZXNYD-Z02);the Joint Project of Luzhou Municipal Government-Southwest Medical University(2016LZXNYD-J12)
- DOI：10.16016/j.1000-5404.201708137
  CLC： R341; R394.1; R734.35
- Received：24 August 2017，
  
  Revised：2017-09-06，
  
  Published：30 December 2017
- 稿件说明：
移动端阅览
Xinshen LI, Jianhua PENG, Jinwei PANG, et al. Effects of apolipoprotein E mimetic peptide COG1410 on central autophagy and apoptosis after subarachnoid hemorrhage in mice[J]. Journal of Third Military Medical University, 2017, 39(24): 2366-2373.
DOI：

Xinshen LI, Jianhua PENG, Jinwei PANG, et al. Effects of apolipoprotein E mimetic peptide COG1410 on central autophagy and apoptosis after subarachnoid hemorrhage in mice[J]. Journal of Third Military Medical University, 2017, 39(24): 2366-2373. DOI： 10.16016/j.1000-5404.201708137.

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(

＜0.05)，并在24 h达到高峰(

＜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(

＜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(

＜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(

＜0.01)，COG1410的干预能显著改善SAH组的Garcia评分(15.17±0.75)(

＜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

① Compared with the sham group

the autophagy in the injured cerebral hemisphere was increased at 6 h after SAH (

0.05)

peaked at 24 h (

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 (

0.05). ② In the phase of EBI after SAH

the apoptosis status in t

he 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 (

0.05).③The neurological score was significantly lower in the model group than the sham group (11.17±1.83

16.50±1.05

0.01)

but the score was notably improved after the administration of COG1410 (15.17±0.75

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.

关键词

Keywords

references

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