Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200065, People's Republic of China.
J Mol Neurosci. 2020 Nov;70(11):1797-1807. doi: 10.1007/s12031-020-01572-1. Epub 2020 Jun 8.
Methylene blue (MB) has a protective effect on cognitive decline caused by chronic hypoperfusion, but the specific mechanism is not clear. This article aims to determine whether MB protects vascular neurons through PI3K/Akt and plays a role in improving cognitive impairment. Molecular biological methods, the hippocampal neuronal density test, the hippocampal vascular network density test, and dynamic enhanced magnetic resonance imaging (MRI) were used to detect the blood-brain barrier permeability and Evans blue leakage rate in the hippocampus. We also observed and evaluated the changes in the above results after administration of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway protein inhibitor LY294002. There were significant differences for cerebral blood flow (CBF) between the chronic cerebral hypoperfusion (CCH) + MB group (100 ml/100 g/min) and the CCH group (60 ml/100 g/min, P < 0.05). After using LY294002, the CBF of the CCH + MB + LY294002 group dropped to 82 ml/100 g/min. The vascular density in the CCH + MB group was 23%, which is significantly higher than that in the CCH group (15.1%) (P < 0.05). The vascular density (17.5%) in the CCH + MB + LY294002 group was significantly higher than that in the CCH group but lower than that in the CCH + MB group. Western blotting results showed that one week after intraperitoneal injection of MB, the expression of t-Akt and p-Akt in the CCH + MB group was increased after CCH, and LY294002 partially blocked this up-regulation effect (CCH + MB + LY294002 group). MB is a potential therapy for the relief of mild cognitive impairment associated with CCH, vascular dementia, and Alzheimer's disease.
亚甲蓝（MB）对慢性低灌注引起的认知下降具有保护作用，但具体机制尚不清楚。本文旨在确定 MB 是否通过 PI3K/Akt 保护血管神经元，并发挥改善认知障碍的作用。采用分子生物学方法、海马神经元密度检测、海马血管网络密度检测和动态增强磁共振成像（MRI）检测海马血脑屏障通透性和 Evans 蓝漏率。我们还观察并评价了磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）通路蛋白抑制剂 LY294002 给药后上述结果的变化。慢性脑低灌注（CCH）+MB 组（100ml/100g/min）与 CCH 组（60ml/100g/min）的脑血流（CBF）差异有统计学意义（P<0.05）。使用 LY294002 后，CCH+MB+LY294002 组 CBF 下降至 82ml/100g/min。CCH+MB 组血管密度为 23%，明显高于 CCH 组（15.1%）（P<0.05）。CCH+MB+LY294002 组血管密度（17.5%）明显高于 CCH 组，但低于 CCH+MB 组。Western blot 结果显示，MB 腹腔注射 1 周后，CCH 后 CCH+MB 组 t-Akt 和 p-Akt 表达增加，LY294002 部分阻断了这种上调作用（CCH+MB+LY294002 组）。MB 可能是治疗与 CCH、血管性痴呆和阿尔茨海默病相关的轻度认知障碍的一种潜在疗法。
