Wang Nan, He Jinting, Pan Chengliang, Wang Jiaoqi, Ma Ming, Shi Xinxiu, Xu Zhongxin
Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China.
College of Clinical Medicine, Jilin University, Changchun, China.
Front Neurosci. 2019 Aug 20;13:859. doi: 10.3389/fnins.2019.00859. eCollection 2019.
Chronic cerebral hypoperfusion (CCH) is a main cause of vascular dementia and is also an etiological factor of neurological diseases and mental disorders. However, few treatments are available for CCH, and new medications are needed. In the present study, we employed a rat model of CCH that was based on bilateral common carotid artery occlusion and investigated the therapeutic effects of resveratrol and its detailed mechanism of action. We evaluated neurological deficit scores and performed the Morris water maze test, hematoxylin and eosin staining, TUNEL staining, enzyme-linked immunosorbent assays, and Western blot. Resveratrol reduced neurological deficit scores in CCH rats and reduced pathological damage in the frontal cortex and hippocampus. Resveratrol activated autophagy and inhibited the expression of AKT/mechanistic target of rapamycin (mTOR) signaling pathway-related proteins. Treatment with a phosphoinositide-3 kinase inhibitor reversed the protective effect of resveratrol. These findings suggest that resveratrol improves cognitive function in a rat model of CCH and reduces oxidative stress-induced neuronal damage in the frontal cortex and hippocampus by activating autophagy and inhibiting neuronal apoptosis. These effects may be regulated by the AKT/mTOR signaling pathway.
慢性脑灌注不足（CCH）是血管性痴呆的主要原因，也是神经疾病和精神障碍的病因。然而，针对CCH的治疗方法很少，需要新的药物。在本研究中，我们采用了基于双侧颈总动脉闭塞的CCH大鼠模型，研究了白藜芦醇的治疗效果及其详细作用机制。我们评估了神经功能缺损评分，并进行了莫里斯水迷宫试验、苏木精-伊红染色、TUNEL染色、酶联免疫吸附测定和蛋白质印迹法。白藜芦醇降低了CCH大鼠的神经功能缺损评分，并减轻了额叶皮质和海马体的病理损伤。白藜芦醇激活了自噬并抑制了AKT/雷帕霉素机制性靶标（mTOR）信号通路相关蛋白的表达。用磷脂酰肌醇-3激酶抑制剂治疗可逆转白藜芦醇的保护作用。这些发现表明，白藜芦醇可改善CCH大鼠模型的认知功能，并通过激活自噬和抑制神经元凋亡减轻额叶皮质和海马体中氧化应激诱导的神经元损伤。这些作用可能受AKT/mTOR信号通路调节。
