Orexin-A对缺氧状态下海马神经元的影响及其机制

doi:10.6040/j.issn.1671-7554.0.2015.1024

山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (4): 17-24.doi: 10.6040/j.issn.1671-7554.0.2015.1024

Orexin-A对缺氧状态下海马神经元的影响及其机制

李国华^1,2,池恒¹,邢慧敏²,唐吉友¹

1.山东大学附属千佛山医院神经内科, 山东济南 250014;2.济南市第三人民医院神经内科, 山东济南 250132

收稿日期:2015-10-28 出版日期:2016-04-10 发布日期:2016-04-10
通讯作者: 唐吉友. E-mail:tangjiyou@sohu.com E-mail:tangjiyou@sohu.com
基金资助:
国家自然科学基金(81471345);山东省自然科学基金(2R2012HM068)

Effects and potential mechanism of orexin-A on hippocampal neurons under hypoxia condition

LI Guohua^1,2, CHI Heng¹, XING Huimin², TANG Jiyou¹

1. Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China;
2. Department of Neurology, Third Peoples Hospital of Jinan, Jinan 250132, Shandong, China

Received:2015-10-28 Online:2016-04-10 Published:2016-04-10

摘要/Abstract

摘要： 目的通过建立大鼠海马神经元氧糖剥夺(OGD)模型,探讨orexin-A(OXA)对缺氧状态海马神经元的作用及其潜在机制。方法 Wistar大鼠海马神经细胞分为对照组、氧糖剥夺组(OGD组)、氧糖剥夺加OXA组(OGD+OXA组,包括OGD+OXA 1 nmol/L组、OGD+OXA 3 nmol/L组、OGD+OXA 10 nmol/L组、OGD+OXA 100 nmol/L组)、氧糖剥夺加U0126组(OGD+U0126组)和氧糖剥夺加OXA、U0126组(OGD+OXA +U0126组)。取原代海马神经元培养72 h后,氧糖剥夺以建立缺氧损伤模型,后分别加入不同终浓度的OXA(1、3、10、100 nmol/L),于48 h观察OXA对海马神经元凋亡率的影响;并利用U0126 阻滞ERK_1/2通路,通过Western blotting及细胞凋亡率检测,探究OXA对海马神经元凋亡率影响的分子机制。结果与OGD组相比,OGD+OXA 3 nmol/L组、OGD+OXA 10 nmol/L组和OGD+OXA 100 nmol/L组的细胞凋亡率均显著增加(P<0.01);OGD+OXA 10 nmol/L组和OGD+OXA 100 nmol/L组的细胞凋亡率高于OGD+OXA 3 nmol/L组(P<0.01),而二者之间无统计学差异(P>0.05)。U0126预处理后,OGD+U0126组海马神经元的凋亡率明显低于OGD组(P<0.01);OGD+U0126+OXA组的海马神经元凋亡率明显低于OGD+OXA 100 nmol/L组(P<0.01)。结论高浓度OXA对海马神经元有损害作用,并加重缺氧状态下的神经元损害,其作用机制与OXA过度激活ERK_1/2信号通路有密切关系。

关键词: Orexin-A, 氧糖剥夺, 细胞外调节蛋白激酶, 海马神经元

Abstract: Objective To investigate the effects of orexin-A(OXA)on the hippocampal neurons of Wistar rats in the state of oxygen glucose deprivation(OGD)and its potential mechanism. Methods Hippocampal nerve cells of Wistar rats were divided into the control group, OGD group, OGD+OXA groups(including OGD+OXA 1 nmol/L group, OGD+OXA 3 nmol/L group, OGD+OXA 10 nmol/L group and OGD+OXA 100 nmol/L group), OGD+U0126 group, and OGD+OXA+U0126 group. The hypoxia models of primary hippocampal neurons were built after 72-hour culture, and then different concentrations of OXA(1, 3, 10 and 100 nmol/L)were added in after OGD. The effects of OXA on the apoptotic rate of hippocampus neurons were detected 48 hours later. MAPK/ERK_1/2 pathway was blocked by U0126 to investigate the molecular mechanism. Results Compared with OGD group, the apoptotic rates of hippocampal cells of OGD+OXA 3 nmol/L group, OGD+OXA 10 nmol/L group and OGD+OXA 100 nmol/L group were significantly increased(P<0.01); there was no significant difference between the OGD+OXA 10nmol/L group and OGD+OXA 100 nmol/L group(P>0.05), while the cell apoptotic rate of these two groups were higher than that of OGD+OXA 3 nmol/L group(P<0.01). After U0126 treatment, the apoptotic rate of hippocampal neurons of OGD+U0126 group was significantly lower than that of OGD group(P<0.01), and that of the OGD+U0126+OXA group was lower than OGD+OXA 100 nmol/L group(P<0.01). Conclusion OXA at high concentration can aggravate the damage of 山东大学学报 (医学版)54卷4期 -李国华,等.Orexin-A对缺氧状态下海马神经元的影响及其机制 \=-OGD on hippocampal neurons, which closely associates with the excessively stimulated ERK_1/2 signal pathway by OXA.

Key words: Extracellular signal-regulated kinase, Oxygen glucose deprivation, Hippocampal neurons, Orexin-A

中图分类号:

李国华,池恒,邢慧敏,唐吉友. Orexin-A对缺氧状态下海马神经元的影响及其机制[J]. 山东大学学报（医学版）, 2016, 54(4): 17-24.

LI Guohua, CHI Heng, XING Huimin, TANG Jiyou. Effects and potential mechanism of orexin-A on hippocampal neurons under hypoxia condition[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(4): 17-24.

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Orexin-A对缺氧状态下海马神经元的影响及其机制

Effects and potential mechanism of orexin-A on hippocampal neurons under hypoxia condition

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