α-细辛醚对Fmr1基因敲除小鼠跳台行为和海马P-Akt表达的影响

摘要

Objective To discuss the therapeutic effects of the memory defect and possible mechanism ofα-asarone,by observing its in-fluence on jumping avoidance test on KO mice and expression of P-Akt. Metheds 4 -week-old homozygous( - / -)FVB FMR1 gene knock addition to the type( KO)and 4-week-old homozygous(/)FVB wild-type( WT)inbred mice were divided into seven groups:blank control group,negative control group( saline group),α-asarone treatment group 3 mg/kg group,6 mg/kg group,9 mg/kg group,12 mg/kg group,24 mg/kg group,with 16 KO mice in each group,a total of 112;and 17 WT mice in each group,a total of 119. The total number of KO and WT mice was 231. 4-week-old mice accepted intraperitoneal injection of saline andα-asarone for 6 days,and in the 7th day(first day) after intraperitoneal injection for 30 minutes,step down test was performed and passive avoidance and jumping latency and the number of errors were detected;In the 8th day(second day)after intraperitoneal injection for 30 minutes,step down test was performed and passive avoidance and jumping latency and the number of errors were detected;the 9th day after intraperitoneal injection for 30 minutes,the expression of the P-Akt, and Akt in the hippocampus of the brain were observed by Western blot method. Results Step down test results:Jumping latency of the KO mice negative control group,3 mg/kg,6 mg/kg,9 mg/kg and 12 mg/kg treatment group was significantly higher than the control group( P ﹤0. 05), but there was statistically significant difference in 24 mg/kg group( P ﹥0. 05). The number of errors of KO mice in each group has no significant difference( P ﹥0. 05). There was no significant difference when compared different indicators of WT mice( P ﹥0. 05). Hippocampus P-Akt expression of KO mice was significantly reduced than those in WT mice. Expression of Akt in KO and WT mice has no statistically significantly difference( P ﹥0. 05). P-Akt expression of KO mice in each treatment group has no significant difference( P ﹥0. 05). Conclusion Part dose of the α-asarone can improve the KO mice jumping behavior. Damage of Akt pathway in KO mice may be one of the possible reasons for the KO mice impaired learning and memory.%目的通过观察α-细辛醚对Fmr1基因敲除小鼠（ KO鼠）跳台行为和海马磷酸化蛋白激酶B（ P-Akt）表达的影响，初步探讨α-细辛醚对KO鼠学习记忆缺陷的治疗作用及其可能的机制。方法采用4周龄纯合子（-/-）FVB Fmr1基因敲除型及4周龄纯合子（＋/＋）FVB野生型（ WT）近交系小鼠小鼠共计231只。KO及WT小鼠各分7组，分别为：空白对照组，阴性对照组（生理盐水组），α-细辛醚治疗组3 mg/kg组，6 mg/kg组，9 mg/kg组，12 mg/kg 组，24 mg/kg组，KO小鼠每组16只；WT小鼠每组17只。4周龄小鼠予连续腹腔注射生理盐水及α-细辛醚6 d，第7天腹腔注射30 min后行跳台实验（第1天），测定小鼠避暗及跳台潜伏期和错误次数，第8天腹腔注射30 min后行跳台实验（第2天），测定小鼠避暗及跳台潜伏期和错误次数，第9天腹腔注射30 min后取脑海马，并通过Western blot观察小鼠海马内P-Akt及Akt表达。结果跳台实验结果：KO小鼠阴性对照组，3 mg/kg，6 mg/kg，9 mg/kg及12 mg/kg用药组的跳台潜伏期较空白对照组有明显增高（ P ﹤0.05），而在24 mg/kg组，虽然潜伏期较空白组有增加，但是无统计学意义差异（ P ﹥0.05）。KO小鼠各组的跳台实验错误次数之间无统计学差异（ P ﹥0.05）。WT小鼠腹腔注射生理盐水及不同剂量α-细辛醚后，各组间的跳台实验的潜伏期及错误次数均无统计学差异（ P ﹥0.05）。KO小鼠海马中的P-Akt均较WT小鼠明显减少。而Akt的表达在KO及WT小鼠中均无统计学意义的变化（ P ﹥0.05）。用药后KO小鼠各用药组之间P-Akt表达变化无统计学差异（ P ﹥0.05）。结论部分α-细辛醚剂量可改善KO小鼠的跳台行为， KO小鼠的Akt通路可能受损，这可能是导致KO小鼠学习记忆受损的可能原因之一。