Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University.
Department of Anesthesiology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University.
Neuroreport. 2024 Oct 2;35(14):925-935. doi: 10.1097/WNR.0000000000002083. Epub 2024 Jul 30.
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.
在这项研究中，建立了术后认知功能障碍（POCD）小鼠模型，以观察炎症、血脑屏障通透性和髓鞘的变化，并探讨人参皂苷 Rg1 预处理改善 POCD 综合征的作用。通过异氟烷麻醉下胫骨骨折内固定，建立 15-18 月龄小鼠的 POCD 模型。手术前连续 14 天腹腔内注射人参皂苷 Rg1（40mg/kg/天）进行预处理。通过 Morris 水迷宫检测认知功能。通过 ELISA 检测海马、皮质和血清中白细胞介素-1β和肿瘤坏死因子-α的含量。通过 Evans 蓝观察血脑屏障通透性。通过定量 PCR 和 Western blot 分析海马中 2'，3'-环核苷酸 3'-磷酸二酯酶（CNPase）、髓鞘碱性蛋白（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。通过 Western blot 分析海马中 ZO-1 和 Wnt1 的蛋白表达水平。最后，通过免疫荧光检测海马中 CNPase 和 MBP 的定位。人参皂苷 Rg1 可预防 POCD、外周和中枢炎症以及血脑屏障渗漏，并逆转老年小鼠中 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改善老年小鼠术后认知功能，其具体机制可能与 Wnt/β-连环蛋白通路有关。
