本研究建立术后认知功能障碍（POCD）小鼠模型，观察炎症、血脑屏障通透性和髓鞘的变化，并探讨人参皂苷Rg1预处理对改善POCD综合征的作用。异氟烷麻醉下采用胫骨骨折内固定法建立15～18月龄小鼠POCD模型。术前预处理为连续腹腔注射人参皂苷Rg1(40 mg/kg/天)14天。采用Morris水迷宫检测认知功能。采用ELISA法检测海马、皮质及血清中白细胞介素-1β、肿瘤坏死因子-α的含量。伊文思蓝观察血脑屏障的通透性。通过定量PCR和蛋白质印迹分析海马中2',3'-环核苷酸3'-磷酸二酯酶(CNPase)、髓磷脂碱性蛋白(MBP)、β-连环蛋白和细胞周期蛋白D1的mRNA水平和蛋白表达水平。采用蛋白质印迹法分析海马ZO-1和Wnt1蛋白表达水平。最后，通过免疫荧光检测CNPase和MBP在海马的定位。人参皂苷Rg1可以预防POCD、外周和中枢炎症以及血脑屏障渗漏，并逆转老年小鼠ZO-1、CNPase、MBP和Wnt通路相关分子的下调。临床前研究表明，人参皂苷Rg1通过保护血脑屏障和髓鞘来改善老年小鼠术后认知功能，其具体机制可能与Wnt/β-catenin通路有关。版权所有©2024 Wolters Kluwer Health, Inc.保留权利。

In this study, the postoperative cognitive dysfunction (POCD) mouse model was established to observe the changes in inflammation, blood-brain barrier permeability, and myelin sheath, and we explore the effect of ginsenoside Rg1 pretreatment on improving POCD syndrome. The POCD model of 15- to 18-month-old mice was carried out with internal fixation of tibial fractures under isoflurane anesthesia. Pretreatment was performed by continuous intraperitoneal injection of ginsenoside Rg1(40 mg/kg/day) for 14 days before surgery. The cognitive function was detected by the Morris water maze. The contents of interleukin-1β and tumor necrosis factor-α in the hippocampus, cortex, and serum were detected by ELISA. The permeability of blood-brain barrier was observed by Evans blue. The mRNA levels and protein expression levels of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin basic protein (MBP), beta-catenin, and cyclin D1 in the hippocampus were analyzed by quantitative PCR and western blotting. The protein expression levels of ZO-1 and Wnt1 in the hippocampus were analyzed by western blotting. Finally, the localizations of CNPase and MBP in the hippocampus were detected by immunofluorescence. Ginsenoside Rg1 can prevent POCD, peripheral and central inflammation, and blood-brain barrier leakage, and reverse the downregulation of ZO-1, CNPase, MBP, and Wnt pathway-related molecules in aged mice. Preclinical studies suggest that ginsenoside Rg1 improves postoperative cognitive function in aged mice by protecting the blood-brain barrier and myelin sheath, and its specific mechanism may be related to the Wnt/β-catenin pathway.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.