【摘要】 目的探讨糖原合成酶激酶3(GSK3)抑制剂氯化锂对FMR1基因敲除(KO)小鼠的高架十字迷宫行为的干预作用及机制。方法给90只30日龄FMR1基因敲除小鼠连续5d腹腔注射不同剂量的氯化锂,用药第6天进行高架十字迷宫行为学实验,通过录像机录像,然后用Smart软件分析录像,观察能否改善KO鼠的高架十字迷宫的表型;同时通过免疫印迹技术检测KO及野生型(WT)鼠的海马和皮层中GSK3β和磷酸化GSK3β(p-GSK3β)的变化。结果在高架十字迷宫实验中,与WT组小鼠比较,KO组小鼠的运动性、兴奋性、探索性明显增强,且KO组小鼠在开放区域的活动时间、次数以及路程均明显高于WT组。KO鼠用氯化锂后,在开放区域的活动时间、次数以及路程均减低,差异具有统计学意义(P<0.05)。免疫印迹实验结果显示,KO鼠p-GSK3β表达比WT鼠少;用氯化锂后,KO鼠p-GSK3β表达增加。WT鼠用氯化锂后,开放区域活动时间、次数以及路程有较少改善,p-GSK3β表达也有增加。未使用氯化锂的KO鼠与WT鼠相比,总GSK3β表达无明显差异,KO鼠和WT鼠使用氯化锂后,总GSK3β无明显改变,P>0.05。结论 GSK3β的抑制剂氯化锂能改善KO鼠的高架十字迷宫表型,对KO鼠有治疗作用,其机制可能与氯化锂导致的p-GSK3β表达增加有关。更多还原

【Abstract】 Objective To study the intervention and mechanism of glycogen synthase kinase 3(GSK3) inhibitor,lithium chloride,on the elevated plus-maze behavior of fragile X mental retardation 1(FMR1) knockout mice.Methods Ninety 30-days-old FMR1 knockout(KO) mice were used in this study and lithium chloride was intraperitoneally and continuously injected for 5 days.Elevated plus-maze test was processed in day 6.We monitored the trace of the mice and analyzed it with a software named Smart,to observe whether lithium chloride could ameliorate the phenotype of KO mice in elevated plus-maze.We also tested the expression of GSK3β and p-GSK3β in both cortex and hippocampus of KO and wild type(WT) mice with Western blotting.Results In the elevated plus-maze,we observed that,comparing with WT mice,KO mice had significantly higher moveability,excitability and exploratory.KO mice also had more time spent in open arms as well as the entry and total distance than WT mice.After lithium chloride administration,the time spent,entry and total distance of KO mice in the open arms had significantly reduction(P<0.05).In Western blotting test,we found the expression of p-GSK3β of KO mice was less than WT mice.After treated with lithium chloride,KO mice had the increased p-GSK3β expression.WT mice had amelioration in time spent,entry and total distance in the open arms after lithium chloride applied.We observed the increased p-GSK3β expression in the lithium chloride treated WT mice.Compared the KO control with the WT control,there was no significant difference in total GSK3β expression.After lithium chloride administration,there were no significance changes in total GSK3β expression(P>0.05).Conclusion The function of lithium which ameliorates elevated plus-maze behaviors may relate to its effect that is to increase the expression of p-GSK3β,and may have therapeutic effects in FMR1 knockout mice.更多还原