瑞马唑仑和咪达唑仑对健康老龄大鼠认知功能影响的比较  

Comparison of effects of remazolam and midazolam on cognitive function in healthy aged rats

作　　者：史媛[1] 蒋毅 董贝贝[1] 谢克亮[1] 于泳浩[1] Shi Yuan;Jiang Yi;Dong Beibei;Xie Keliang;Yu Yonghao(Department of Anesthesiology,Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院麻醉科,300052

出　　处：《中华麻醉学杂志》2020年第9期1089-1092,共4页Chinese Journal of Anesthesiology

摘　　要：目的比较瑞马唑仑和咪达唑仑对健康老龄大鼠认知功能的影响。方法清洁级健康老龄雄性Wistar大鼠30只,18~20月龄,体重600~650 g,采用随机数字表法分为3组(n=10):对照组(C组)、咪达唑仑组(M组)和瑞马唑仑组(R组)。尾静脉置管后,M组给予咪达唑仑25 mg/kg负荷剂量,维持剂量3~6 mg·kg-1·h-1;R组给予瑞马唑仑25 mg/kg负荷剂量,维持剂量60~120 mg·kg-1·h-1,连续5 d,每天连续输注8 h,C组给予等量生理盐水。停药后第1、3和7天进行Y迷宫实验,记录新异臂停留时间和各个臂穿梭次数总和。进行场景恐惧和声音恐惧条件实验,计算僵直时间比率;末次Y迷宫实验后即刻处死大鼠取海马组织,采用Western blot法测定Tau蛋白、p-Tau蛋白和载脂蛋白E(ApoE)的表达。结果与C组比较,M组和R组新异臂停留时间缩短,各个臂穿梭次数总和减少,场景恐惧条件实验的僵直时间比率降低,海马Tau蛋白、p-Tau蛋白和ApoE表达上调(P<0.05);与M组比较,R组新异臂停留时间延长,各个臂穿梭次数总和增加,场景恐惧条件实验的僵直时间比率升高,海马Tau蛋白、p-Tau蛋白和ApoE表达下调(P<0.05)。结论与咪达唑仑比较,瑞马唑仑对健康老龄大鼠认知功能的影响较小,与上调海马ApoE表达,导致Tau蛋白磷酸化的程度不同有关。Objective To compare of the effects of remazolam versus midazolam on cognitive function in healthy aged rats.Methods Thirty Wistar clean-grade healthy male rats,aged 18-20 months,weighing 600-650 g,were divided into 3 groups(n=10 each)using a random number table method:control group(group C),midazolam group(group M),and remimazolam group(group R).After the caudal vein was implanted,midazolam was given in a loading dose of 25 mg/kg and a maintenance dose of 3-6 mg·kg-1·h-1 in group M,remimazolam was given in a loading dose of 25 mg/kg and a maintenance dose of 60-120 mg·kg-1·h-1,and remimazolam was continuously infused for 8 h every day for 5 consecutive days in group R,while the equal volume of normal saline was given instead in group C.Y-maze test was performed on days 1,3 and 7 after administration,and the time of staying at the novel arm and the total number of entries into each arm were recorded.The contextual and tone-cued fear conditioning tests were performed,and the ratio of time spent freezing was calculated.Immediately after the last Y maze test,the rats were sacrificed,and the hippocampal tissues were obtained,and the expression of Tau protein,p-Tau protein and apolipoprotein E(ApoE)was determined by Western blot.Results Compared with group C,the time of staying at the novel arm was significantly shortened,the total number of entries into each arm was reduced,and the ratio of time spent freezing induced by context was decreased,and the expression of Tau,p-Tau and ApoE was up-regulated in M and R groups(P<0.05).Compared with group M,the time of staying at the novel arm was significantly prolonged,the total number of entries into each arm was increased,and the ratio of time spent freezing induced by context was increased,and the expression of Tau,p-Tau and ApoE was down-regulated in group R(P<0.05).Conclusion Compared with midazolam,remazolam has less effect on the cognitive function in healthy aged rats,which is related to the up-regulation of hippocampal ApoE expression and further leads to differe

关 键 词：苯二氮䓬类 认知 老年人 

分 类 号：R614[医药卫生—麻醉学]