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CART 抑制 OGD 诱导培养大鼠皮层神经元
内质网应激
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邱彬
1
,贾增强
2
,刘丽冰
2
,王亚宸
1
,祝世功
1**
基金项目:高等学校博士学科点专项科研基金资助课题(项目编号:20090001110060)
作者简介:邱彬(1983 年-),男,博士研究生,活性肽与神经保护
通信联系人:祝世功(1955-),男,教授,活性肽与神经保护. E-mail: sgzhu@bjmu.edu.cn
(1. 北京大学医学部生理学与病理生理学系,北京,100191; 5
2. 山东省潍坊医学院,潍坊,261053)
摘要:目的:探讨可卡因-安非他命调节转录肽(CART)对糖氧剥夺(OGD)诱导的大鼠
皮层神经元内质网应激的作用。方法:18 天 SD 大鼠胚胎(E18)皮层神经元原代培养 8 天,
采用糖氧剥夺法(OGD)诱导神经元损伤。用 MTT 法检测细胞的存活率、western blotting10
方法检测内质网应激反应标志分子(GRP78,caspase 12 和 CHOP)。结果:与对照组比较,
OGD 组的神经元存活率显著降低(P < 0.05),内质网应激标志分子 GRP78、CHOP 和
caspase12 表达增多(P < 0.05)。CART 预处理组神经元的细胞活性明显高于 OGD 组(P <
0.05),GRP78、CHOP 和 caspase12 表达明显低于 OGD 组(P < 0.05)。结论:CART 通
过抑制内质网应激反应减轻 OGD 诱导的大鼠皮层神经元损伤。 15
关键词:神经保护;可卡因-安非他命调节转录肽;糖氧剥夺;内质网应激;
中图分类号:R363
Inhibitory effect of CART on OGD-induced endoplasmic
reticulum stress in rat cortical neurons 20
Qiu Bin
1
, Jia Zengqiang
2
, Liu Libing
2
, Wang Yachen
1
, Zhu Shigong
1
(1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking
University Health Science Center, Beijing, 100191;
2. Weifang Medical University, Weifang, 261053)
Abstract: Object: To investigate the effect of cocaine- and amphetamine-regulated transcript 25
(CART) on oxygen and glucose deprivation (OGD)-induced endoplasmic reticulum stress in rat
cortical neurons. Method: The primary cultured cortical neurons were established from embryonic
rats (E18). The neuronal injury was induced by OGD method. The cell survival was analysed by
MTT method, and the expression of endoplasmic reticulum stress (ER stress) markers (GRP78,
CHOP and caspase12) were determined by western blotting. Results: Compared to Control group, 30
neuronal survival was obviously decreased in OGD group (P < 0.05), while expression of ER
stress markers (GRP78, CHOP and caspase12) were significantly upregulated (P < 0.05). In
CART pretreatment group, cell survival was remarkably enhanced (P < 0.05), while expression of
GRP78, CHOP and caspase12 was siginicantly reduced (P < 0.05) compared to OGD group.
Conclusion: CART ameliorates OGD-induced injury by ER stress inhibition in rat cortical 35
neurons.
Key words: neuroprotection; CART; OGD; endoplasmic reticulum stress;
0 引言:
可卡因-安非他命调节转录肽(CART)是一种神经内分泌多肽,参与多种生理病理过程,40
包括摄食、应激反应、奖赏等
[1]
。近年研究证实,CART 不仅能够促进离体培养的海马神经
元存活
[2]
,还具有神经保护作用。已有文献证明,CART 能够通过增强线粒体 ATP 合成抑
制糖氧剥夺(OGD)诱导的小鼠原代培养皮层神经元损伤
[3]
。另有文献证实,OGD 损伤时
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