中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (2): 143-152.doi: 10.4103/1673-5374.125343

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

海马天冬氨酸:术后认知功能障碍的生物标志?

  

  • 收稿日期:2013-06-27 出版日期:2014-01-10 发布日期:2014-01-10
  • 基金资助:

    国家自然科学基金(30871306)

Aspartic acid in the hippocampus: a biomarker for postoperative cognitive dysfunction

Rong Hu1, Dong Huang1, Jianbin Tong2, Qin Liao1, Zhonghua Hu1, Wen Ouyang1   

  1. 1 Department of Anesthesia, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China
    2 Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
  • Received:2013-06-27 Online:2014-01-10 Published:2014-01-10
  • Contact: Wen Ouyang, Ph.D., Professor, Department of Anesthesia, Third Xiangya Hospital, Central South University, Changsha 410078, Hunan Province, China, ouyangwen133@vip.sina. com.

摘要:

实验用2%异氟醚和80%的氧气麻醉老年大鼠2h建立术后认知功能障碍模型,24h后Y迷宫测试结果显示异氟醚麻醉后老年大鼠的短期记忆明显损害。气相色谱质谱分析结果显示术后认知功能障碍大鼠海马区的天冬氨酸,N,N-二乙基乙酰胺,N-乙基乙酰胺,苹果酸和阿拉伯糖酸明显增高,且天冬氨酸,N,N-二乙基乙酰胺,N-乙基乙酰胺和苹果酸水平与认知功能障碍呈正相关。可见海马组织代谢产物的变化参与了异氟醚麻醉后认知功能障碍的形成。为了进一步验证该结果,实验对海马神经元细胞进行了离体培养,并加入100 µmol/L天冬氨酸进行干预,结果显示天冬氨酸可损害海马神经元细胞。提示海马组织中的天冬氨酸浓度是预测术后认知功能障碍的发生和病程进展的可靠标志。

关键词: 神经再生, 脑损伤, 麻醉, 术后认知功能障碍, 异氟醚, 海马, 代谢产物, 代谢组学, 气相色谱质谱分析, 天冬氨酸, NSFC

Abstract:

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid            (100 µmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Key words: nerve regeneration, brain impairment, anesthesia, postoperative cognitive dysfunction, isoflurane, hippocampal metabolites, metabonomics, gas chromatography-mass spectrometry, aspartic acid, NSFC grant, neural regeneration