中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (9): 825-832.doi: 10.3969/j.issn.1673-5374.2013.09.007

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

异氟烷诱发发育期大脑神经元凋亡的机制

  

  • 收稿日期:2012-12-12 修回日期:2013-01-19 出版日期:2013-03-25 发布日期:2013-03-25

Isoflurane-induced neuronal apoptosis in developing hippocampal neurons

Hongliang Liu1, Tijun Dai2, Weitao Guo3   

  1. 1 Department of Anesthesiology, Chongqing Cancer Institute/Cancer Hospital, Chongqing 400030, China
    2 Department of Pharmacology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China
    3 Department of Orthopedics Affiliated Hospital, Guangdong Medical College, Zhanjiang 524000, Guangdong Province, China
  • Received:2012-12-12 Revised:2013-01-19 Online:2013-03-25 Published:2013-03-25
  • Contact: Hongliang Liu, ☆, Ph.D., Associate professor, Department of Anesthesiology, Chongqing Cancer Institute/Cancer Hospital, Chongqing 400030, China, liuhl75@163.com.

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摘要：

实验假设P2X7受体可能是异氟烷的作用靶位，以此观察嘌呤P2X7受体和三磷酸肌醇受体对异氟烷诱发大鼠胚胎海马神经元钙超载及神经元凋亡的影响。结果显示，异氟烷可诱发大鼠神经元凋亡并显著升高细胞内钙浓度，而应用嘌呤P2X7受体拮抗剂或去除胞外钙离子结合使用三磷酸肌醇受体拮抗剂可完全抑制异氟烷作用，单独去除胞外钙离子或使用三磷酸肌醇受体拮抗剂可部分拮抗异氟烷的作用。异氟烷可直接激活嘌呤P2X7受体，但不影响嘌呤P2X7受体的表达。结果说明，异氟烷诱发大鼠发育期海马神经元凋亡的机制与嘌呤P2X7受体介导钙内流和三磷酸肌醇受体介导钙释放导致细胞内钙超载有关。

关键词: 神经再生, 基础实验, 异氟烷, 受体, 嘌呤P2X7, 三磷酸肌醇, 钙稳态失衡, 凋亡, 发育期大脑, 海马, 大鼠

Abstract:

We hypothesized that the P2X7 receptor may be the target of isoflurane, so we investigated the roles of the P2X7 receptor and inositol triphosphate receptor in calcium overload and neuronal apoptosis induced by isoflurane in cultured embryonic rat hippocampal neurons. Results showed that isoflurane induced widespread neuronal apoptosis and significantly increased cytoplasmic Ca2+. Blockade of P2X7 receptors or removal of extracellular Ca2+ combined with blockade of inositol triphosphate receptors completely inhibited apoptosis or increase in cytoplasmic Ca2+. Removal of extracellular Ca2+ or blockade of inositol triphosphate receptor alone could partly inhibit these effects of isoflurane. Isoflurane could directly activate P2X7-gated channels and induce inward currents, but did not affect the expression of P2X7 receptor protein in neurons. These findings indicate that the mechanism by which isoflurane induced neuronal apoptosis in rat developing brain was mediated by intracellular calcium overload, which was caused by P2X7 receptor mediated calcium influx and inositol triphosphate receptor mediated calcium release.

Key words: neural regeneration, brain injury, isoflurane, P2X7 receptor, inositol triphosphate receptor, calcium homeostasis disturbance, neurodegenerative disease, apoptosis, developing brain, hippocampus, grants-supported paper, photographs-containing paper, neuroregeneration