【摘要】 目的:探讨GSK3抑制剂氯化锂对FMR1基因敲除小鼠的自主活动的干预作用及机制。方法:通过对90只30日龄FMR1基因敲除小鼠连续腹腔注射不同剂量氯化锂5d,行自主活动行为学实验,观察能否改善KO鼠的过度活动的表型;同时利用免疫印迹技术检测KO及WT鼠的海马和皮层的GSK3β和P-GSK3β的变化。结果:在自主活动行为学实验中,KO鼠的活动次数比WT鼠的活动次数增多而站立次数比WT鼠减少,差异具有统计学意义(P<0.05);使用氯化锂后,KO鼠的活动次数明显减少及站立次数明显增多,差异均有统计学意义(P<0.05);免疫印迹实验结果:KO鼠P-GSK3β表达比WT鼠少,用氯化锂后,KO鼠P-GSK3β的表达增多。KO鼠和WT鼠使用氯化锂后,总的GSK3β无明显改变(P>0.05)。结论:GSK3β的抑制剂氯化锂能改善KO鼠的活动过度的表型,可能与氯化锂导致的P-GSK3β的表达增加有关,对FMR1基因敲除小鼠有治疗作用。更多还原

【Abstract】 Objective To study the intervention and mechanism of lithium(chloride GSK3 inhibitor) on spontaneous activity of FMR1 knockout(KO)mice.Methods 90 30-day-old FMR1 KO mice were applied and lithium chloride was intraperitoneal injected continuously for 5 days.We observed whether lithium chloride could ameliorate the phenotype of KO mice in spontaneous activity test.We also tested the expression of GSK3β and P-GSK3β in both cortex and hippocampus of KO and WT mice by western blot.Results In the spontaneous activity test,KO mice had more motion and less standing than WT mice,which had statistical significance(P < 0.05).After lithium chloride administration,KO mice had decreased motion and increased standing(P < 0.05).In Western Blot test,there was less P-GSK3β expression in KO mice than in WT mice;while lithium chloride was employed,the expression of P-GSK3β was raised in KO mice.After lithium chloride were administrated in both KO and WT mice,the total GSK3β expression had no significant changes(P > 0.05).Conclusion The function of lithium,which ameliorates spontaneous activity test behaviors,may be related to its effect of increasing the expression of P-GSK3β,and may have therapeutic effect in FMR1 knockout mice.更多还原