中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (5): 894-902.doi: 10.4103/1673-5374.268927

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

迷迭香酸促进髓鞘再生改善缺氧缺血性脑损伤后的认知障碍

  

  • 出版日期:2020-05-15 发布日期:2020-06-01
  • 基金资助:

    江苏省自然科学基金项目(BK20171180

Rosmarinic acid ameliorates hypoxia/ischemia induced cognitive deficits and promotes remyelination

Man Li1, Miao-Miao Cui1, Nwobodo Alexander Kenechukwu1, Yi-Wei Gu2, Yu-Lin Chen1, Si-Jing Zhong3, Yu-Ting Gao4, Xue-Yan Cao2, Li Wang2, Fu-Min Liu1, Xiang-Ru Wen5#br#   

  1. 1 Department of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
    2 Department of Urology, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
    3 Xuzhou Medical University Clinical Medical College, Xuzhou, Jiangsu Province, China
    4 Department of Clinical Laboratory, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
    5 Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • Online:2020-05-15 Published:2020-06-01
  • Contact: Fu-Min Liu,liufumin820@163.com; Xiang-Ru Wen, MS,xiangruwen123@163.com.
  • Supported by:
    This work was supported by the Natural Science Foundation of Jiangsu Province of China, No. BK20171180 (to XRW).

摘要:

迷迭香酸是一种能从迷迭香、紫苏、丹参等多种中草药中提取的酯类,研究显示其对脑缺血/再灌注损伤等多种疾病具有保护作用,但其是否也能对缺氧损伤引起的白质纤维变化和认知缺陷产生影响,目前尚无确切公认信息。(1)实验首先结扎出生3d大鼠的右颈总动脉2h,而后以37℃水浴饲养30min,再以8%O2和92%N2低氧干预30min,建立围产期缺氧缺血脑损伤模型,然后连续5d腹腔注射迷迭香酸(20mg/kg)。出生后22d时发现,迷迭香酸可改善由缺氧缺血脑损伤诱导的运动、焦虑以及学习和空间记忆障碍;(2)此外发现迷迭香酸还促进脑室下区中少突胶质细胞祖细胞的增殖。且在缺氧缺血脑损伤后,迷迭香酸可在一定程度上逆转脑白质结构胼胝体中髓磷脂碱性蛋白的下调以及髓鞘的缺失;(3)迷迭香酸能部分减缓少突胶质细胞标志物Olig2和髓磷脂碱性蛋白表达的减少以及少突胶质细胞凋亡标志物Id2(分化/DNA结合因子2)的增加;(4)结果表明,迷迭香酸可通过改善胼胝体中的髓鞘再生来改善围产期缺氧缺血脑损伤后的认知功能障碍。实验于2017-9-16经徐州医科大学实验动物伦理委员会批准,批准号20161636721。

orcid: 0000-0002-9282-8176 (Xiang-Ru Wen)

关键词: 缺氧缺血, 迷迭香酸, 认知功能障碍, 髓鞘, 髓鞘再生, 胼胝体, 髓磷脂碱性蛋白, 分化/DNA结合因子2

Abstract: Rosmarinic acid, a common ester extracted from Rosemary, Perilla frutescens, and Salvia miltiorrhiza Bunge, has been shown to have protective effects against various diseases. This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury. The right common carotid artery of 3-day-old rats was ligated for 2 hours. The rats were then prewarmed in a plastic container with holes in the lid, which was placed in 37°C water bath for 30 minutes. Afterwards, the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models. The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days. At 22 days after birth, rosmarinic acid was found to improve motor, anxiety, learning and spatial memory impairments induced by hypoxia/ischemia injury. Furthermore, rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone. After hypoxia/ischemia injury, rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure. Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2. These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum. This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University, China (approval No. 20161636721) on September 16, 2017.

Key words: cognitive dysfunction, corpus callosum, differentiation/DNA binding factor 2, hypoxia/ischemia, myelin basic protein, myelin sheath,
remyelination,
rosmarinic acid