Department of Pharmacology, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University.
Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical University.
Biol Pharm Bull. 2020;43(9):1315-1323. doi: 10.1248/bpb.b20-00112.
Vascular dementia (VD) is a common neurodegenerative disease, and the cognitive dysfunction is a major manifestation of VD. Lots of evidences showed that beta-amyloid (Aβ) deposition and neuroinflammation act as vital elements in the progress of VD. The previous studies showed that osthole (OST) can improve the cognitive function of VD and Alzheimer's disease (AD). However, the effect of OST on Aβ in VD brain is still unclear. Chronic cerebral hypoperfusion (CCH) of rats were used to investigate the effect of OST on Aβ through nod-like receptor protein 3 (NLRP3) inflammasome in this study. Morris Water Maze and Y-maze were used to test the spatial learning, memory and working abilities. Hematoxylin-eosin (H&E) and Nissl staining were used to observe the morphology and number of hippocampal neurons. Immunofluorescence staining was used to observe the number of microglia activated. Western blot was used to detect the expression of proteins. The study results showed that OST obviously enhanced the spatial learning, memory and working abilities induced by modified bilateral common carotid artery occlusion (BCCAO) in rats, improved the pathological damage of hippocampal neurons induced by BCCAO in rats, inhibited the activation of microglia induced by BCCAO in rats. Furthermore, this study also discovered that OST reduced Aβ deposition in VD hippocampus via inhibition the NLRP3 inflammasome. Together, these results suggest that OST reduces Aβ deposition via inhibition NLRP3 inflammasome in microglial in VD.
血管性痴呆（VD）是一种常见的神经退行性疾病，认知功能障碍是 VD 的主要表现之一。大量证据表明，β-淀粉样蛋白（Aβ）沉积和神经炎症是 VD 进展的重要因素。先前的研究表明，蛇床子素（OST）可以改善 VD 和阿尔茨海默病（AD）的认知功能。然而，OST 对 VD 大脑中 Aβ的影响尚不清楚。本研究通过 nod-like receptor protein 3 (NLRP3) 炎性小体，使用大鼠慢性大脑低灌注（CCH）来研究 OST 对 Aβ的影响。Morris 水迷宫和 Y 迷宫用于测试空间学习、记忆和工作能力。苏木精-伊红（H&E）和尼氏染色用于观察海马神经元的形态和数量。免疫荧光染色用于观察激活的小胶质细胞数量。Western blot 用于检测蛋白质的表达。研究结果表明，OST 明显增强了改良双侧颈总动脉闭塞（BCCAO）诱导的大鼠空间学习、记忆和工作能力，改善了 BCCAO 诱导的大鼠海马神经元的病理损伤，抑制了 BCCAO 诱导的大鼠小胶质细胞的激活。此外，本研究还发现 OST 通过抑制 NLRP3 炎性小体减少 VD 海马中的 Aβ沉积。综上所述，这些结果表明 OST 通过抑制小胶质细胞中的 NLRP3 炎性小体减少 VD 中的 Aβ 沉积。
