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小檗碱通过调节 ERK/Nrf2 通路来防止慢性脑低灌注诱导的认知障碍和海马损伤。

Berberine protects against chronic cerebral hypoperfusion-induced cognitive impairment and hippocampal damage via regulation of the ERK/Nrf2 pathway.

机构信息

Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China; Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.

Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

出版信息

J Chem Neuroanat. 2022 Sep;123:102119. doi: 10.1016/j.jchemneu.2022.102119. Epub 2022 Jun 11.

DOI:10.1016/j.jchemneu.2022.102119
PMID:35697268
Abstract

Vascular cognitive impairment caused by chronic cerebral hypoperfusion (CCH) seriously affects the quality of life of elderly patients and places a great burden on society and family. With the development of traditional Chinese medicine (TCM), TCM approaches to the prevention and treatment of senile ischemic cerebrovascular disease has received increasing attention. In this study, rats with bilateral common carotid artery occlusion (BCCAO) were treated with berberine (BBR). Their learning and memory function, neuronal injury and repair, the extracellular regulatory protein kinase (ERK)/nuclear factor-E2-related factor 2 (Nrf2) signaling pathway, and impairment and improvement of the blood-brain barrier (BBB) were evaluated. This study found that BBR can alleviate the pathological injury to the brain, reduce neuronal loss and promote neuronal cell survival after CCH by interfering with the ERK/Nrf2 signaling pathway. BBR can reduce BBB injury in CCH rats by inhibiting the expression of VEGF-A and MMP-9 in plasma, which reveals a protective effect of BBR on vascular cognitive impairment. This study provides a new research direction for BBR in the treatment of ischemic cerebrovascular disease.

摘要

慢性脑低灌注引起的血管性认知障碍(CCH)严重影响老年患者的生活质量,给社会和家庭带来沉重负担。随着中医药的发展,中医药防治老年缺血性脑血管病受到越来越多的关注。本研究采用小檗碱(BBR)对双侧颈总动脉闭塞(BCCAO)大鼠进行治疗,评估其学习记忆功能、神经元损伤与修复、细胞外调节蛋白激酶(ERK)/核因子-E2 相关因子 2(Nrf2)信号通路以及血脑屏障(BBB)的损害和改善。本研究发现,BBR 通过干扰 ERK/Nrf2 信号通路,可以减轻 CCH 后的病理性脑损伤,减少神经元丢失,促进神经元细胞存活。BBR 还可以通过抑制血浆中 VEGF-A 和 MMP-9 的表达来减轻 CCH 大鼠的 BBB 损伤,从而揭示了 BBR 对血管性认知障碍的保护作用。本研究为 BBR 治疗缺血性脑血管病提供了新的研究方向。

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