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目的探讨氯化锂治疗是否能改善Fmr1基因敲除小鼠(ko鼠)学习跳台行为及糖原合成酶激酶3β(GSK3β)的活性。方法选用30日龄的Fmr1基因敲除小鼠(ko鼠)及同日龄的野生型小鼠(wt鼠),两种小鼠均分别给予生理盐水和氯化锂30、60、90、120、200 mg/kg。观察用药后ko鼠及wt鼠分别在行为学跳台实验中的潜伏期和错误次数。同时用免疫印迹观察ko及wt鼠的海马和皮层的GSK3β和磷酸化GSK3β(P-GSK3β)的表达。结果与未治疗的wt鼠比较,未治疗的ko鼠跳台实验中的潜伏期时间短,错误次数增加,存在学习跳台障碍;免疫印迹实验结果:ko鼠P-GSK3β表达比wt鼠少。氯化锂治疗能够恢复ko鼠的学习跳台行为及增加P-GSK3β的表达量。氯化锂最佳使用剂量为30 mg/kg。结论锂能改善ko鼠的学习跳台能力,可能与锂改善P-GSK3β的表达增加有关,对Fmr1基因敲除小鼠有治疗作用。
Objective To investigate whether lithium chloride treatment can improve learning behavior and glycogen synthase kinase 3β (GSK3β) activity in Fmr1 knockout mice (ko mice). Methods 30-day-old Fmr1 knockout mice (ko mice) and wild-type mice (wt mice) of the same age were selected. Both mice were given normal saline and lithium chloride 30,60,90,120, 200 mg / kg. Observe the latency and error times of ko mice and wt mice in behavioral jump-table experiment after administration. At the same time, the expression of GSK3β and phosphorylated GSK3β (P-GSK3β) in hippocampus and cortex of ko and wt mice was observed by immunoblot. Results Compared with untreated WK rats, the incubation time of untreated ko rats was short and the number of mistakes increased. There was learning jumping obstacle. Western blot results showed that the expression of P-GSK3β in ko mice was less than that in wt rats. Lithium chloride treatment can restore ko rat learning jumping behavior and increase the expression of P-GSK3β. The best dosage of lithium chloride is 30 mg / kg. Conclusion Lithium can improve ko rat learning and jumping ability, may be related to the lithium to improve the expression of P-GSK3β, Fmr1 knockout mice have therapeutic effect.