首页|甘草酸苷联合艾司氯胺酮对小鼠围手术期神经认知障碍的影响及其机制

甘草酸苷联合艾司氯胺酮对小鼠围手术期神经认知障碍的影响及其机制

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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(TLR4)、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1d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-KB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DG区均检测到HMGB1在细胞质中表达;与PND组相比,甘草酸苷+艾司氯胺酮组术后第1天小鼠海马CA1区及DG区HMGB1表达明显减少.结论 甘草酸苷联合亚麻醉剂量艾司氯胺酮可改善小鼠围手术期神经认知功能及海马神经炎症,其机制可能与抑制HMGB1/TLR4/NF-κB信号通路相关.
Effect and its mechanism of glycyrrhizin combined with esketamine on perioperative neurocognitive disorders in mice
Objective To explore the effect and its mechanism of glycyrrhizin combined with esketamine on perioperative neurocogni-tive 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 results showed that compared with blank group,the expression levels of IL-1β,TNF-α,HMGB1,TLR-4 and NF-κB in the hippocampus at the same time point after operation were significantly increased in the other groups(P<0.05).Compared with PND group,the expression levels of IL-1β,TNF-α,HMGB1,TLR-4 and NF-κB were significantly decreased in the hippocampus in glycyrrhizin group,esketamine group and glycyrrhizin+esketamine group at the same time point after operation(P<0.05).Compared with glycyrrhizin group and esketamine group,the expression levels of IL-1β,TNF-α,HMGB1,TLR-4 and NF-κB were significantly decreased in the hippocampus in glycyrrhizin+esketamine group at the same time point after operation(P<0.05).Immu-nofluorescence results showed that compared with blank group,the expression of HMGB1 in the hippocampus CA1 and DG regions was significantly increased in PND group at day 1 after operation,and HMGB1 expression was detected in the cytoplasm in both hippocampus CA1 and DG regions.Compared with PND group,the expression of HMGB1 was significantly decreased in the hippocampus CA1 and DG region of mice in glycyrrhizin+esketamine group at day 1 after operation.Conclusion Glycyrrhizin combined with a subanesthetic dose of esketamine can improve the perioperative neurocognitive function and the hippocampal neuroinflammation in mice by inhibiting the HMGB1/TLR4/NF-κB signaling pathway.

glycyrrhizinesketamineneurocognitive disordersHMGB1TLR-4

王彬、杨建新、李月、吉郝斌、孟治寿

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山西医科大学麻醉学教研室,太原 030001

山西医科大学第二医院疼痛科

甘草酸苷 艾司氯胺酮 神经认知障碍 高迁移率族蛋白质类 Toll样受体4

山西省应用基础研究计划-面上自然基金项目山西省卫生健康委科研项目山西省研究生教育创新项目

201901D11137220190432022Y433

2024

山西医科大学学报
山西医科大学

山西医科大学学报

CSTPCD
影响因子:0.931
ISSN:1007-6611
年,卷(期):2024.55(1)
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