Nicotinamide riboside rescues angiotensin --induced cerebral small vessel disease in mice
Nicotinamide riboside rescues angiotensin --induced cerebral small vessel disease in mice
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DOI：
10.1111/cns.13276
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发表时间：
2020-01-14
影响因子：
5.5
通讯作者：
Feng, Hua
中科院分区：
文献类型：
--
作者：
Li, Cheng-Cheng;Chen, Wei-Xiang;Feng, Hua
目的高血压是脑小血管病（CSVD）的主要病因。目前，CSVD的治疗方法有限。烟酰胺核苷（NR）可以保护神经退行性疾病中的血管损伤和认知障碍。本研究旨在探讨NR对血管紧张素（Ang -）诱导的CSVD的保护作用。方法采用C57 BL/6小鼠灌胃血管紧张素-1（Ang -1），并在食物中添加NR，连续28天，观察NR对CSVD的影响。然后，检测短期记忆、血脑屏障（BBB）完整性和内皮功能。还评价了小动脉损伤和胶质细胞活化。结果Ang -1灌胃28 d后，小鼠短期记忆功能下降，血脑屏障渗漏，claudin-5表达减少，小窝介导的内吞增加。此外，Ang -1还可降低小动脉中α-平滑肌肌动蛋白（α-SMA）的表达，增加小动脉中增殖细胞核抗原（PCNA）的表达，降低白色物质中神经丝200（NF 200）和髓鞘碱性蛋白（MBP）的表达。NR可抑制Ang -1诱导的CSVD相关损伤。此外，NR给药显著降低了血管周围的胶质细胞活化。结论NR可通过保护BBB完整性、血管重构、神经炎症和白色损伤（white matter injury，HHT）相关的认知功能障碍来减轻Ang -1诱导的CSVD。
Aims Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin - (Ang -)-induced CSVD were evaluated. Methods To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang -, and NR was added to the food of the mice for 28 days. Then, short-term memory, blood-brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated. Results Our data showed that mice infused with Ang - exhibited decreased short-term memory function and BBB leakage due to decreased claudin-5 expression and increased caveolae-mediated endocytosis after 28 days. Furthermore, Ang - decreased the expression of alpha-smooth muscle actin (alpha-SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD-related damages induced by Ang - were inhibited by NR administration. Moreover, NR administration significantly reduced glial activation around the vessels. Conclusion Our results indicated that NR administration alleviated Ang --induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)-associated cognitive impairment.