Effect of APOE alleles and apoE-mimetic peptide COG1410 on early neuron apoptosis after <em>in vitro</em> traumatic brain injury

Jiang Yong; Sun Xiaochuan; Chen Ligang; Gui Li

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Effect of APOE alleles and apoE-mimetic peptide COG1410 on early neuron apoptosis after in vitro traumatic brain injury

更新时间：2025-01-15

- Effect of APOE alleles and apoE-mimetic peptide COG1410 on early neuron apoptosis after in vitro traumatic brain injury
- Journal of Army Medical University Vol. 36, Issue 6, Pages: 548-552(2014)
- 作者机构：
  
  1. 泸州医学院附属医院神经外科
  2. 重庆医科大学附属第一医院神经外科
- 作者简介：
- 基金信息：
- DOI：
  CLC： R329.28;R341;R651.102
- Published：2014，
  
  Published Online：30 March 2014，
- 稿件说明：
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JIANG YONG, SUN XIAOCHUAN, CHEN LIGANG, et al. Effect of APOE alleles and apoE-mimetic peptide COG1410 on early neuron apoptosis after in vitro traumatic brain injury. [J]. Journal of army medical university, 2014, 36(6): 548-552.
DOI：

JIANG YONG, SUN XIAOCHUAN, CHEN LIGANG, et al. Effect of APOE alleles and apoE-mimetic peptide COG1410 on early neuron apoptosis after in vitro traumatic brain injury. [J]. Journal of army medical university, 2014, 36(6): 548-552. DOI：

摘要

目的探讨载脂蛋白E（APOE代表基因，apoE代表蛋白）亚型特异性及其短肽与早期凋亡的相关性，以期明确APOE亚型影响脑创伤病情转归及预后的病理机制。方法采用稳定表达人APOE各等位基因的APOE敲除鼠的神经干细胞，优化诱导分化条件，构建神经元/胶质细胞共培养体系及细胞划痕损伤模型。通过Annexin V/PI联合流式细胞技术检测损伤后各组细胞早期凋亡率，分析人APOE各等位基因及其短肽影响继发性神经细胞损伤的差异。结果成功构建携带人源性APOE各亚型的细胞划痕损伤模型；伤后24 h时间点各组细胞早期凋亡率较6、12 h明显增高（

0.05），且人APOEε4组较其余亚型组早期凋亡率明显增高（

0.05）。在伤后24 hapoE短肽COG1410可显著降低各亚型组早期凋亡率（

0.01）。结论 APOEε4携带者可能通过早期凋亡导致脑创伤急性期病情加重。而apoE短肽COG1410可通过降低早期凋亡发挥神经保护作用。

Abstract

Objective To elucidate the mechanism mediating the effects of apolipoprotein E (APOE for gene

apoE for protein) alleles and apoE-mimetic peptide COG1410 on early apoptosis in an

in vitro

model of experimental traumatic brain injury. Methods Eukaryotic expression vectors carrying individual APOE alleles (ε2

ε3

ε4) were transferred into neural stem cells (NSCs) derived from APOE knockout mice. An

in vitro

neuronal/glial co-culture model of mechanical injury was developed using a contr

olled scratch. Flow cytometry was performed to analyze the correlations among APOE genotypes

apoE-mimetic peptide COG1410 and early apoptosis. Results Early apoptosis after injury was observed in all groups

which was significantly higher at 24 h after injury than at 6 h and 12 h after injury (

0.05). The group transfected with APOEε4 showed more significant early apoptosis 24 h after injury as compared to the groups transfected with APOEε2 or APOEε3 (

0.05). Furthermore

decreases of early apoptosis were detected in the groups treated with apoE-mimetic peptide COG1410 at 24 h after injury (

0.01). Conclusion APOEε4-trasfected NSCs showing a higher rate of early apoptosis indicates that the patients with APOEε4 may suffer aggravation of brain trauma in acute stage due to early apoptosis. Our results also identify the early neuroprotective effect of apoE-mimetic peptide COG1410.

关键词

载脂蛋白E短肽创伤性脑损伤体外模型早期凋亡

Keywords

apolipoprotein EapoE-mimetic peptidetraumatic brain injuryin vitro modelearly apoptosis

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Effect of APOE alleles and apoE-mimetic peptide COG1410 on early neuron apoptosis after in vitro traumatic brain injury

DOI：

摘要

Abstract

关键词

Keywords

references