利多卡因基于TASK-3通道诱导老龄小鼠认知功能障碍研究

Explore of Lidocaine induced postoperative cognitive dysfunction in aged mice based on TASK-3 channe

目的探究TASK-3通道在利多卡因(Lidoc)诱导老龄小鼠术后认知功能障碍(POCD)中的作用。方法野生型(WT)小鼠与TASK-3敲除(TASK-3^(-/-))小鼠各20只,随机分为WT组,WT+Lidoc组,TASK-3^(-/-)组,TASK-3^(-/-)+Lidoc组。取WT+Lidoc组,TASK-3^(-/-)+Lidoc组小鼠每天皮下注射40mg·kg^(-1) Lidoc麻醉,6h后分别开展水迷宫实验或者跳台实验,共7d。取小鼠脑组织分别开展免疫组化染色、苏木精-伊红染色、TUNEL染色、树突棘染色、电生理测试。结果与WT组相比,WT+Lidoc组小鼠水迷宫中逃避潜伏期明显增加,首次到达平台时间增加,穿越平台次数与平台象限停留时间明显减少,跳台潜伏期与跳台错误次数明显增加。然而,与TASK-3^(-/-)组相比,TASK-3^(-/-)+Lidoc组小鼠水迷宫实验与跳台时间指标没有明显改变。此外,与WT组相比,WT+Lidoc组小鼠脑组织中Caspase-3表达明显增加,神经元状态明显损伤,TUNEL阳性细胞数明显增加。与此同时,Lidoc造成小鼠海马神经元树突棘密度明显减少,fEPSP斜率明显减少。然而,与TASK-3^(-/-)组相比,TASK-3^(-/-)+Lidoc组小鼠Caspase-3表达并没有明显改变,神经元状态正常且TUNEL阳性细胞数没有变化。与此同时,小鼠神经元树突棘状态和fEPSP斜率没有影响。结论Lidoc诱导老龄小鼠POCD可能是激活TASK-3通道造成Caspase-3表达增加实现。

Objective To explore the role of TASK-3 channel in Lidocaine(Lidoc)-induced postoperative cognitive dysfunction(POCD)in aged mice.Methods 20 wild-type(WT)mice and 20 TASK-3 knockout(TASK 3)mice were randomly divided into WT group,WT+Lidoc group,TASK-3^(-/-)group,TASK-3^(-/-)+Lidoc group.Mice in the WT+Lidoc group and TASK-3^(-/-)+Lidoc group were subcutaneously injected with 40 mg·kg^(-1)Lidoc every day for anesthesia.After 6 hours,the water maze test or step down test was carried out for a total of 7 days.Then,the mice were sacrificed and the brains were used for immunohistochemical staining,HE staining,TUNEL staining,dendritic spines staining,and electrophysiological tests.Results Compared with the WT group,the escape latency in the water maze of the WT+Lidoc mice increased significantly,the time of the first to platform increased,the number of platform crossings and residence time in the platform quadrant decreased significantly,and the latency and the errors of step down test increased significantly.However,compared with TASK-3^(-/-)group,TASK-3^(-/-)+Lidoc group mice water maze experiment and step down test indexes did not change.In addition,compared with the WT group,the expression of Caspase-3 in the brains of the mice in the WT+Lidoc group was significantly increased,the neuron status was significantly damaged,and the number of TUNEL positive cells was significantly increased.At the same time,Lidoc caused a significant decrease in the dendritic spine density of hippocampal neurons in mice,and a significant decrease in the fEPSP slope.However,compared with the TASK-3^(-/-)group,the expression of Caspase-3 in the TASK-3^(-/-)+Lidoc group did not change significantly,the neuron status was normal and the number of TUNEL positive cells did not change.At the same time,the dendritic spines of mouse neurons and the slope of fEPSP had no effect.Conclusion Lidoc may activate TASK-3 channel and increase the expression of Caspase-3 that lead to POCD in aged mice.