中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (1): 210-216.doi: 10.4103/1673-5374.314320

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

鼻内胰岛素给药改善脑出血小鼠的神经功能损伤

  

  • 出版日期:2022-01-05 发布日期:2021-09-22

Intranasal insulin ameliorates neurological impairment after intracerebral hemorrhage in mice

Yuan Zhu1, 2, #, Yi Huang1, 2, #, Jin Yang3, Rong Tu1, 2, Xin Zhang1, 2, Wei-Wei He1, 2, Chang-Yue Hou1, 2, Xiao-Ming Wang1, 2, Ju-Ming Yu1, 2, *, Guo-Hui Jiang1, 2, *#br#   

  1. 1Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China; 2Institute of Neurological Diseases, North Sichuan Medical College, Nanchong, Sichuan Province, China; 3Department of Intensive Care Unit, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China
  • Online:2022-01-05 Published:2021-09-22
  • Contact: Guo-Hui Jiang, MD, neurodoctor@163.com; Ju-Ming Yu, MD, yujuming1963@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81971220; and a grant from the Science and Technology Department of Sichuan Province of China, No. 2018JY0236 (both to GHJ).

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摘要：

鼻内胰岛素脑给药在治疗阿尔茨海默病和缺血性卒中方面显示出神经保护作用，但其是否也可作为脑出血的神经保护剂及潜在机制知之甚少。（1）实验用自体血构建脑出血小鼠模型，并在造模后每天2次鼻腔滴入胰岛素0.5，1，2 IU，直到术后24或72h；（2）见1 IU鼻内胰岛素治疗可明显减少脑出血后的血肿体积和脑水肿，并降低血脑屏障通透性和减轻神经元变性损伤，同时改善神经行为缺陷，提高生存率；（3）经鼻内胰岛素治疗的脑出血小鼠，血肿周围组织中磷酸化AKT和磷酸化糖原合酶激酶3β的表达水平显著升高，表明鼻内胰岛素脑给药可通过AKT/糖原合酶激酶3β信号通路保护实验性脑出血小鼠的神经功能。实验于2019年1月7日经川北医学院伦理委员会批准（批准号NSMC（A）2019（01））。

https://orcid.org/0000-0002-1267-2221 (Guo-Hui Jiang); https://orcid.org/0000-0003-1964-4634 (Ju-Ming Yu)

关键词: 胰岛素, 脑出血, 鼻内给药, 神经障碍, AKT, 糖原合酶激酶3β, 血脑屏障, 神经保护, 脑血肿, 脑水肿, 神经元变性

Abstract: In Alzheimer’s disease and ischemic stroke, intranasal insulin can act as a neuroprotective agent. However, whether intranasal insulin has a neuroprotective effect in intracerebral hemorrhage and its potential mechanisms remain poorly understood. In this study, a mouse model of autologous blood-induced intracerebral hemorrhage was treated with 0.5, 1, or 2 IU insulin via intranasal delivery, twice per day, until 24 or 72 hours after surgery. Compared with saline treatment, 1 IU intranasal insulin treatment significantly reduced hematoma volume and brain edema after cerebral hemorrhage, decreased blood-brain barrier permeability and neuronal degeneration damage, reduced neurobehavioral deficits, and improved the survival rate of mice. Expression levels of p-AKT and p-GSK3β were significantly increased in the perihematoma tissues after intranasal insulin therapy. Our findings suggest that intranasal insulin therapy can protect the neurological function of mice after intracerebral hemorrhage through the AKT/GSK3β signaling pathway. The study was approved by the Ethics Committee of the North Sichuan Medical College of China (approval No. NSMC(A)2019(01)) on January 7, 2019.

Key words: AKT, blood-brain barrier, brain edema, glycogen synthase kinase-3, hematoma, insulin, intracerebral hemorrhage, intranasal insulin, neurological impairment, neuronal degeneration, neuroprotection