摘要
目的探讨甘草酸苷联合艾司氯胺酮通过调节海马区高迁移率族蛋白B1(HMGB1)信号通路对小鼠围手术期神经认知障碍(PND)的影响及相关机制。方法将小鼠分为空白组、PND组、甘草酸苷组、艾司氯胺酮组、甘草酸苷+艾司氯胺酮组,每组24只。本实验通过Morris水迷宫评估小鼠空间学习记忆能力,各组小鼠分别于术前1 d,术后1,3,7 d行定位航行实验记录逃避潜伏期,术后第7天行空间探索实验记录目标象限穿梭次数。ELISA法检测术前1 d,术后1,3,7 d各组小鼠海马区白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、HMGB1、Toll样受体4(TLR-4)、核因子κB(NF-κB)表达含量。免疫荧光实验检测空白组、PND组、甘草酸苷+艾司氯胺酮组术后第1天小鼠海马区HMGB1表达情况。结果各组术前1 d各指标比较差异无统计学意义(P>0.05)。Morris水迷宫结果显示:与空白组相比,其他组术后同时点逃避潜伏期均延长(P<0.05),术后第7天穿越平台次数均减少(P<0.05);与PND组相比,甘草酸苷组、艾司氯胺酮组和甘草酸苷+艾司氯胺酮组术后同时点逃避潜伏期缩短(P<0.05),术后第7天穿越平台次数增多(P<0.05);与甘草酸苷组和艾司氯胺酮组相比,甘草酸苷+艾司氯胺酮组术后同时点逃避潜伏期缩短(P<0.05),术后第7天穿越平台次数增多(P<0.05)。ELISA结果显示:与空白组相比,其余组术后同时点海马区IL-1β、TNF-α、HMGB1、TLR-4、NF-κB表达含量均明显升高(P<0.05);与PND组相比,甘草酸苷组、艾司氯胺酮组和甘草酸苷+艾司氯胺酮组术后同时点海马区IL-1β、TNF-α、HMGB1、TLR-4、NF-κB表达含量明显降低(P<0.05);与甘草酸苷组和艾司氯胺酮组相比,甘草酸苷+艾司氯胺酮组术后同时点海马区IL-1β、TNF-α、HMGB1、TLR-4、NF-κB表达含量明显降低(P<0.05)。免疫荧光结果显示:与空白组相比,PND组小鼠术后第1天海马CA1区及DG区HMGB1表达明显增多,且在海马CA1区及
Objective To explore the effect and its mechanism of glycyrrhizin combined with esketamine on perioperative neurocognitive disorders(PND)in mice by modulating the high mobility group protein B1(HMGB1)signaling pathway in the hippocampus.Methods The mice were divided into blank group,PND group,glycyrrhizin group,esketamine group,and glycyrrhizin+esketamine group,with 24 mice in each group.The spatial learning and memory ability of mice was assessed by Morris water maze,and the escape latency was recorded in the positioning navigation experiment at day 1 before operation and at day 1,3,7 after operation,and the number of target quadrant shuttles was recorded in the spatial probe test at day 7 after operation.ELISA was used to detect the levels of interleukin-1β(IL-1β),tumour necrosis factor-α(TNF-α),HMGB1,Toll-like receptor 4(TLR-4),and nuclear factor-κB(NF-κB)in hippocampus of the mice in each group at day 1 before operation and at day 1,3,7 after operation.Immunofluorescence was performed to detect the expression of HMGB1 in the hippocampus of mice in blank group,PND group,and glycyrrhizin+esketamine group at day 1 after operation.Results There was no significant difference in all indexes among the groups at day 1 before operation(P>0.05).Morris water maze test showed that compared with blank group,the escape latency in the other groups was prolonged at the same time point after operation(P<0.05),and the number of crossing the platform at day 7 after operation was significantly decreased(P<0.05).Compared with PND group,the escape latency was shortened in glycyrrhizin group,esketamine group and glycyrrhizin+esketamine group at the same time point after operation(P<0.05),and the number of crossing the platform was increased at day 7 after operation(P<0.05).Compared with glycyrrhizin group and esketamine group,the escape latency was shortened in glycyrrhizin+esketamine group at the same time point after operation(P<0.05),and the number of crossing platforms was increased at day 7 after operation(P<0.05).ELISA
作者
王彬
杨建新
李月
吉郝斌
孟治寿
WANG Bin;YANG Jianxin;LI Yue;JI Haobin;MENG Zhishou(Department of Anesthesiology,Shanxi Medical University,Taiyuan 030001,China;Department of Pain,Second Hospital of Shanxi Medical University)
出处
《山西医科大学学报》
CAS
2024年第1期76-84,共9页
Journal of Shanxi Medical University
基金
山西省应用基础研究计划-面上自然基金项目(201901D111372)
山西省卫生健康委科研项目(2019043)
山西省研究生教育创新项目(2022Y433)。
