中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (9): 937-942.doi: 10.4103/1673-5374.133145

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

反复热惊厥致未成熟大鼠海马神经元及突触损伤:1,6-二磷酸果糖的保护效应

  

  • 收稿日期:2014-03-20 出版日期:2014-05-20 发布日期:2014-05-20
  • 基金资助:

    西安交大医学创新基金资助(gh0203214)和陕西省人民医院革新基金项目。国家自然科学基金(30901600)。陕西省科技攻关项目(2006k14-g12,2005k14-g7)。

Repeated febrile convulsions impair hippocampal neurons and cause synaptic damage in immature rats: neuroprotective effect of fructose-1,6-diphosphate

Jianping Zhou 1, Fan Wang 2, Jun Zhang 3, Hui Gao 4, Yufeng Yang 5, Rongguo Fu 6   

  • Received:2014-03-20 Online:2014-05-20 Published:2014-05-20
  • Contact: Jianping Zhou, M.D., Department of Pediatrics, the Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China, pediatricianzjp@163.com.
  • Supported by:

    This study was financially supported by the Medical Innovations Fund of Xi’an Jiaotong University, No. GH0203214; Shaanxi Provincial People’s Hospital Incubator Fund Projects; the National Natural Science Foundation of China, No. 30901600; Shaanxi Provincial Scientific and Technological Research Projects, No. 2006K14-G12, 2005K14-G7.

摘要:

鉴于1,6-二磷酸果糖有促进细胞代谢的作用。我们假设1,6-二磷酸果糖能减轻由热性惊厥引起的神经元损伤。实验选取相当于人类3-5岁的21日龄未成熟大鼠,应用热水浴法建立反复热性惊厥大鼠模型,于反复热性惊厥诱发前90 min,向大鼠腹腔注射高、低剂量的1,6-二磷酸果糖(每100 g体质量100,50 mg)。末次惊厥后24 h发现,高、低剂量1,6-二磷酸果糖均能延缓大鼠惊厥发生的潜伏期并缩短惊厥持续时间,而且高剂量1,6-二磷酸果糖可显著减轻惊厥严重程度。透射电镜下观察,高剂量1,6-二磷酸果糖腹腔注射可减轻反复热性惊厥大鼠海马CA1区线粒体肿胀、粗面内质网脱颗粒以及高尔基体扩张,能显著缩小突触间隙宽度,能增加突触活性带长度及突触后致密区厚度及突触界面曲率。结果提示1,6-二磷酸果糖对反复热性惊厥致未成熟大鼠海马神经元及突触损伤有保护作用。

关键词: 神经再生, 脑损伤, 热性惊厥, 1,6-二磷酸果糖, 海马, 惊厥发作, 线粒体, 粗面内质网, 高尔基体, 电子显微镜, 动物模型, 国家自然科学基金

Abstract:

Fructose-1,6-diphosphate is a metabolic intermediate that promotes cell metabolism. We hypothesize that fructose-1,6-diphosphate can protect against neuronal damage induced by febrile convulsions. Hot-water bathing was used to establish a repetitive febrile convulsion model in rats aged 21 days, equivalent to 3–5 years in humans. Ninety minutes before each seizure induction, rats received an intraperitoneal injection of low- or high-dose fructose-1,6-diphosphate (500 or 1,000 mg/kg, respectively). Low- and high-dose fructose-1,6-diphosphate prolonged the latency and shortened the duration of seizures. Furthermore, high-dose fructose-1,6-diphosphate effectively reduced seizure severity. Transmission electron microscopy revealed that 24 hours after the last seizure, high-dose fructose-1,6-diphosphate reduced mitochondrial swelling, rough endoplasmic reticulum degranulation, Golgi dilation and synaptic cleft size, and increased synaptic active zone length, postsynaptic density thickness, and synaptic interface curvature in the hippocampal CA1 area. The present findings suggest that fructose-1,6-diphosphate is a neuroprotectant against hippocampal neuron and synapse damage induced by repeated febrile convulsion in immature rats.

Key words: nerve regeneration, brain injury, febrile convulsions, fructose-1,6-diphosphate, hippocampus, seizures, mitochondria, rough endoplasmic reticulum, Golgi complex, electron microscope, animal model, NSFC grant, neural regeneration