Zhu Yuan, Huang Yi, Yang Jin, Tu Rong, Zhang Xin, He Wei-Wei, Hou Chang-Yue, Wang Xiao-Ming, Yu Ju-Ming, Jiang Guo-Hui
Department of Neurology, Affiliated Hospital of North Sichuan Medical College; Institute of Neurological Diseases, North Sichuan Medical College, Nanchong, Sichuan Province, China.
Department of Intensive Care Unit, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China.
Neural Regen Res. 2022 Jan;17(1):210-216. doi: 10.4103/1673-5374.314320.
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.
在阿尔茨海默病和缺血性卒中中,鼻内胰岛素可作为一种神经保护剂。然而,鼻内胰岛素在脑出血中是否具有神经保护作用及其潜在机制仍知之甚少。在本研究中,采用自体血诱导的脑出血小鼠模型,通过鼻内给药0.5、1或2国际单位胰岛素,每天两次,持续至术后24或72小时。与生理盐水治疗相比,1国际单位鼻内胰岛素治疗显著减少了脑出血后的血肿体积和脑水肿,降低了血脑屏障通透性和神经元变性损伤,减少了神经行为缺陷,并提高了小鼠的存活率。鼻内胰岛素治疗后,血肿周围组织中p-AKT和p-GSK3β的表达水平显著升高。我们的研究结果表明,鼻内胰岛素治疗可通过AKT/GSK3β信号通路保护脑出血后小鼠的神经功能。本研究于2019年1月7日获得中国川北医学院伦理委员会批准(批准号:NSMC(A)2019(01))。