中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (6): 1052-1061.doi: 10.4103/1673-5374.300456

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

短暂吸入七氟醚可减轻新生大鼠缺氧缺血性脑损伤后神经胶质瘢痕的形成

  

  • 出版日期:2021-06-15 发布日期:2020-12-31
  • 基金资助:

    本研究得到国家自然科学基金项目（81671311, 81870838）；辽宁省重点研究发展计划（2018225004）；盛京医院优秀科研基金（201708）

Brief inhalation of sevoflurane can reduce glial scar formation after hypoxic-ischemic brain injury in neonatal rats

Qiu-Shi Gao, Ya-Han Zhang, Hang Xue, Zi-Yi Wu, Chang Li, Ping Zhao*    

  1. Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Ping Zhao, MD, PhD, zhaop@sj-hospital.org or zhaoping_sj@163.com.
  • Supported by:
    This study was supported by the National Nature Science Foundation of China, Nos. 81671311, 81870838; the Key Research and Development Program of Liaoning Province of China, No. 2018225004; and the Outstanding Scientific Fund of Shengjing Hospital of China, No. 201708 (all to PZ). 

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摘要：

既往研究显示，七氟醚后处理对缺氧缺血损伤提供神经保护作用，并改善啮齿动物发育中大脑的学习和记忆功能。实验使用经典Rice-Vannucci模型诱导出生后第7天大鼠的缺氧缺血损伤，然后以2 L/min流速吸入2.4％的七氟醚30min进行治疗。结果显示：(1)七氟醚后处理可显著改善缺氧缺血性脑损伤大鼠的学习和记忆功能，减少星形胶质细胞过度增生和胶质瘢痕形成，增加树突棘数量并保护海马的组织形态；(2)七氟醚后处理还能减少缺氧诱导因子1α的泛素化连接酶VHL，同时增加DJ-1表达。而在缺氧缺血损伤前30min，左侧脑室注射1.52μg缺氧诱导因子1α抑制剂YC-1（Lificiguat）则可逆转七氟醚的神经保护作用；(3)结果说明七氟醚可有效缓解缺氧缺血后海马星形胶质细胞的增生，并减少由胶质瘢痕形成引起的学习和记忆障碍，其作用机制可能与上调了DJ-1的表达，降低缺氧诱导因子1α的泛素化，稳定了缺氧诱导因子1α的表达有关。该研究于2016年11月9日获得中国医科大学实验动物保护委员会的批准（批准号2016PS337K）。

https://orcid.org/0000-0001-6392-5391 (Ping Zhao)

关键词: 中枢神经系统, 脑, 脑损伤, 模型, 大鼠, 体内, 损伤, 修复, 保护, 再生, 可塑性

Abstract: Previous studies have demonstrated that sevoflurane postconditioning can provide neuroprotection after hypoxic-ischemic injury and improve learning and memory function in developing rodent brains. The classical Rice-Vannucci model was used to induce hypoxic-ischemic injury, and newborn (postnatal day 7) rats were treated with 2.4% sevoflurane for 30 minutes after hypoxic-ischemic injury. Our results showed that sevoflurane postconditioning significantly improved the learning and memory function of rats, decreased astrogliosis and glial scar formation, increased numbers of dendritic spines, and protected the histomorphology of the hippocampus. Mechanistically, sevoflurane postconditioning decreased expression of von Hippel-Lindau of hypoxia-inducible factor-1α and increased expression of DJ-1. Injection of 1.52 μg of the hypoxia-inducible factor-1α inhibitor YC-1 (Lificiguat) into the left lateral ventricle 30 minutes before hypoxic-ischemic injury reversed the neuroprotection induced by sevoflurane. This finding suggests that sevoflurane can effectively alleviate astrogliosis in the hippocampus and reduce learning and memory impairments caused by glial scar formation after hypoxic-ischemic injury. The underlying mechanism may be related to upregulated DJ-1 expression, reduced ubiquitination of hypoxia-inducible factor-1α, and stabilized hypoxia-inducible factor-1α expression. This study was approved by the Laboratory Animal Care Committee of China Medical University, China (approval No. 2016PS337K) on November 9, 2016.

Key words: brain injury, brain, central nervous system, in vivo, injury, model, plasticity, rat, recovery, regeneration, repair