Tian Yue, Zheng Yangmin, Wang Qi, Yan Feng, Tao Zhen, Zhao Fangfang, Wang Yuqing, Huang Yuyou, Li Fengjuan, Du Yitong, Wang Ningqun, Luo Yumin
Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
CNS Neurol Disord Drug Targets. 2022;21(9):869-879. doi: 10.2174/1871527321666220124140323.
Chronic cerebral hypoperfusion is associated with vascular cognitive impairment, and there are no specific therapeutic agents for use in clinical practice. Berberine has demonstrated good neuroprotective effects in models of acute cerebral ischemia; however, whether it can alleviate cognitive impairment caused by chronic cerebral hypoperfusion has rarely been investigated.
The present study aimed to explore the mechanism by which berberine alleviates cognitive impairment resulting from chronic cerebral hypoperfusion.
Forty-two male Sprague-Dawley rats were randomly divided into three groups: sham, model, and berberine. The models of chronic cerebral hypoperfusion were established via permanent bilateral common carotid artery occlusion (BCCAO). Cognitive function was evaluated using the Morris water maze, while neuronal damage and microglial activation and polarization were evaluated using western blotting and immunofluorescence, respectively. Enzyme-linked immunosorbent assays were used to detect the expression of anti-inflammatory factors including interleukin- 4 (IL-4) and interleukin-10 (IL-10).
Rats exhibited cognitive dysfunction after BCCAO, which was significantly attenuated following the berberine intervention. Levels of synaptophysin and NeuN were decreased in states of chronic cerebral hypoperfusion, during which microglial activation and a transition from the M2 to M1 phenotype were observed. Berberine treatment also significantly reversed these features. Moreover, levels of IL-4 and IL-10 expression increased significantly after berberine treatment.
Berberine may mitigate vascular cognitive dysfunction by promoting neuronal plasticity, inhibiting microglial activation, promoting transformation from an M1 to an M2 phenotype, and increasing levels of IL-4 and IL-10 expression.
慢性脑灌注不足与血管性认知障碍相关，临床实践中尚无特异性治疗药物。黄连素在急性脑缺血模型中已显示出良好的神经保护作用；然而，其是否能减轻慢性脑灌注不足所致的认知障碍鲜有研究。
本研究旨在探讨黄连素减轻慢性脑灌注不足所致认知障碍的机制。
42只雄性Sprague-Dawley大鼠随机分为三组：假手术组、模型组和黄连素组。通过永久性双侧颈总动脉闭塞（BCCAO）建立慢性脑灌注不足模型。采用Morris水迷宫评估认知功能，分别采用蛋白质免疫印迹法和免疫荧光法评估神经元损伤以及小胶质细胞的激活和极化。采用酶联免疫吸附测定法检测抗炎因子白细胞介素-4（IL-4）和白细胞介素-10（IL-10）的表达。
BCCAO术后大鼠出现认知功能障碍，黄连素干预后显著减轻。慢性脑灌注不足状态下，突触素和NeuN水平降低，同时观察到小胶质细胞激活以及从M2型向M1型表型转变。黄连素治疗也显著逆转了这些特征。此外，黄连素治疗后IL-4和IL-10表达水平显著升高。
黄连素可能通过促进神经元可塑性、抑制小胶质细胞激活、促进从M1型向M2型表型转变以及提高IL-4和IL-10表达水平来减轻血管性认知功能障碍。
