中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (9): 1438-1444.doi: 10.4103/1673-5374.191217

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

肌肽可保护慢性脑缺血引起的脑白质损伤

  

  • 收稿日期:2016-08-15 出版日期:2016-09-30 发布日期:2016-09-30
  • 基金资助:
    中国国家自然科学基金项目(81402904);上海交通大学医学院基金(13XJ22001);上海交通大学医学院附属新华医院基金(13YJ11);上海市科委基金(13ZR1426900, 15411963900)

Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion

Jing Ma, Shu-hong Bo, Xiao-tong Lu, A-jing Xu*, Jian Zhang*   

  1. Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Received:2016-08-15 Online:2016-09-30 Published:2016-09-30
  • Contact: A-jing Xu, Ph.D. or Jian Zhang, Ph.D., jeta_xu@hotmail.com or zjpharmacy2014@163.com.
  • Supported by:
    This study was funded by the National Natural Science Foundation of China, No. 81402904; the Foundation of Shanghai Jiao Tong University School of Medicine, No. 13XJ22001; the Foundation of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 13YJ11; a grant from the Science and Technology Commission of Shanghai Municipality of China, No. 13ZR1426900, 15411963900.

摘要:

高表达的肌肽在中枢神经系统中具有清除自由基、抗炎等作用,同时其可通过抗氧化和减少细胞凋亡对缺血或缺氧性脑损伤起到保护作用,因此作者推测肌肽也可对慢性脑缺血引起的脑白质损伤起到保护作用。实验以右侧颈总动脉闭塞造成小鼠脑白质损伤,在损伤前30min及损伤后每隔1d腹腔注射200,500,750 mg/kg肌肽。37d后Klüver-Barrera染色、甲苯胺蓝染色和免疫荧光染色结果显示,200和500 mg/kg肌肽可以明显减轻小鼠胼胝体、内囊、视束白质的损伤,恢复髓鞘碱性蛋白的表达,减少少突胶质细胞缺失,而750 mg/kg肌肽没有类似效果。说明一定剂量的肌肽对慢性脑缺血后白质损伤具有保护作用,该作用可能通过保护少突胶质细胞而实现。 

orcid: 0000-0002-4596-5362 (A-jing Xu), 0000-0002-2119-5172 (Jian Zhang) 

关键词: 神经再生, 皮质下缺血性血管性痴呆, 肌肽, 胼胝体, 神经元, 内囊, 少突胶质细胞, 视束, 脑白质损伤

Abstract: Carnosine is a dipeptide that scavenges free radicals, inhibits in?ammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. Therefore, we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury. White matter damage was induced by right unilateral common carotid artery occlusion in mice. The animals were treated with 200, 500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury. Then, 37 days later, Klüver-Barrera staining, toluidine blue staining and immuno?uorescence staining were performed. Carnosine (200, 500 mg/kg) substantially reduced damage to the white matter in the corpus callosum, internal capsule and optic tract, and it rescued expression of myelin basic protein, and alleviated the loss of oligodendrocytes. However, carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses. These fndings show that carnosine, at a particular dose range, protects against white matter damage caused by chronic cerebral ischemia in mice, likely by reducing oligodendroglial cell loss.

Key words: nerve regeneration, subcortical ischemic vascular dementia, carnosine, corpus callosum, neuron, internal capsule, oligodendrocyte, optic tract, white matter damage, neural regeneration