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褪黑素对新生大鼠缺血缺氧后脑损伤的保护作用 被引量:2

Neuroprotective effect of melatonin on preterm rat after hypoxia-ischemia brain damage
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摘要 目的探讨褪黑素对新生大鼠缺氧缺血性脑损伤(HIBD)的保护作用。方法 Wistar大鼠48只,5日龄时结扎左侧颈总动脉,吸入氧氮混合气体50min制作成HIBD模型,随机分成生理盐水组,褪黑素组,缺血缺氧(HI)+生理盐水组,HI+褪黑素组。褪黑素腹腔注射共3次,每次5 mg/kg,第1次在结扎动脉前,第2次在吸入氧氮混合气体前给予,第3次在HIBD模型制作24h后给予。大鼠在HIBD模型制作后72h被处死,取脑作免疫组化染色,判断脑灰质(microtubule-associatedprotein-2,MAP-2)、脑白质(myelin basic protein,MBP)损伤;HIBD模型制作后7周作Y迷宫记忆功能测试。结果褪黑素能明显减轻HIBD大鼠脑灰质MAP-2和脑白质MBP损伤,还可提高大鼠的长期记忆能力和运动协调能力。结论褪黑素对HIBD大鼠大脑损伤有明显的短期和长期保护作用。 Objective To investigate neuroprotective effect of melatonin on newborn rat brain after hypoxia-ischemia brain damage (HIBD). Methods Forty-eight 5-day-old Wistar rats were randomly divided into physiological saline group, melatonin group, hypoxia-ischemia (HI) + saline group and HI + melatonin group. The HIBD rat models were induced by unilateral ligation of the left common carotid artery followed by 50 rain inhalation of mixed oxygen and nitrogen. Melatonin was intraperitoneally injected three times with a dose of 5mg/kg before artery ligation, before ischemia and after 24h HI immediately. The rats were sacrified after 7211 HI and the immunohistochemical staining was applied to brain tissue. Micrombule-associated protein-2 (MAP-2) and myelin basic protein (MBP) were evaluated as indicators for damages in grey matter and white matter, respectively. The memory abilities of the rats were measured through Y maze test at 7 weeks after HI. Results Melatonin treatment reduced the injury of grey matter and white matter significantly, and improved the long-term memory ability and motor coordination. Conclu- sions Melatonin has a strong short and long-term protection effects on HI damaged brain.
出处 《临床儿科杂志》 CAS CSCD 北大核心 2012年第11期1067-1070,共4页 Journal of Clinical Pediatrics
关键词 褪黑素 缺血缺氧性脑损伤 早产 大鼠 melatonin hypoxic-ischemic brain damage preterm rat
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参考文献17

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同被引文献24

  • 1Dobarro M, Gerenu G, Ramirez MJ. Propranolol reduces cognitive deficits, amyloid and tau pathology in Alzheimer's transgenic mice [J]. Int J Neuropsychopharmacol, 2013, 17 (1): 1-13.
  • 2Okva K, Nevalainen T, Pokk P. The effect of cage shelf on the behavior of male C57BL/6 and BALB/c mice in the ele- vated plus maze test [J]. Lab Anim, 2013,47(3) : 220-222.
  • 3Larroque B, Ancel PY, Marret S, et al. Neurodevelopmental disabilities and special care of 5-year-old children born be- fore 33 weeks of gestation (the EPIPAGE study) : a longitudi- nal cohort study [J]. Lancet, 2008,371(9615): 813-820.
  • 4Mwaniki MK, Atieno M, Lawn JE, et al. Long-term neurode- velopmental outcomes after intrauterine and neonatal insults: a systematic review [J]. Lancet, 2012,379(9814) : 445-452.
  • 5Rees S, Harding R, Walker D. The biological basis of injury and neuroprotection in the fetal and neonatal brain [J]. Int J Dev Neurosci, 2011,29(6) : 551-563.
  • 6Kaur C, Sivakumar V, Ling EA. Melatonin protects periven- tricular white matter from damage due to hypoxia [J]. J Pineal Res, 2010,48(3): 185-193.
  • 7Jim6nez-Rubio G, Ortiz-L6pez L, Benitez-King G. Melato- nin modulates cytoskeletal organization in the rat brain hip- pocampus [J]. Neurosci Lett,2012,511(1):47-51.
  • 8Lee EJ, Lee MY, Chert HY, et al. Melatonin attenuates grayand white matter damage in a mouse model of transient focal cerebral ischemia [J]. J Pineal Res, 2005,38(1):42-52.
  • 9Kaur C, Sivakumar V, Ling EA. Melatonin protects periven- trieular white matter fom damage due to hypoxia [J]. J Pineal Res,2010,48(3): 185-193.
  • 10Hagberg H, Dammann O, Mallard C, et al. Preconditioning and the developing brain [J]. Semin Perinatol, 2004, 28(6): 389-395.

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