目的采用HSF1基因敲除小鼠模型探讨热休克因子1及热休克蛋白(heat shock protein,HSP)在慢性心理应激中对工作记忆的保护作用。方法将热休克因子1(heat shock factor1)基因野生型小鼠(HSF1+/+)和热休克因子1基因敲除小鼠(HSF1-/-)暴露于2个月的慢性心理应激,部分小鼠在暴露于心理应激前给予热休克预处理,2个月后采用T迷宫检测各组小鼠工作记忆,western blots检测和比较HSP72,HSP25表达,采用单因素方差分析和多因素析因设计方差分析对各组小鼠T迷宫转换正确数和HSP72,HSP25表达进行比较。结果 HSF1基因野生型小鼠中,慢性心理应激对T迷宫转换正确数(8.90±0.46)次与对照组(9.58±0.48)次没有明显影响(Ff1.65严0.23,P〉0.05),HSF1基因敲除小鼠中,慢性心理应激引起T迷宫转换正确数(4.00±0.26)次明显低于对照组(7.33±0.43)次,F(1.65)、=32.39,P〈0.05)。同时野生型小鼠心理应激后海马组织中HSP72表达(1.35±0.11),HSP25表达(1.05±0.03)明显高于HSF1基因敲除小鼠(0.23±0.03),(0.26±0.02),均P〈0.05)。热应激也诱导HSP72(1.71±0.05),HSP25(1.33±0.05)表达增加,明显高于HSF1基因敲除小鼠[(0.26±0.03),(0.23±0.08),均P〈0.05],但未发现热应激预处理对T迷宫转换正确数有影响(F(1.65)=0.32,P〉0.05)。结论 HSF1以及慢性心理应激诱导的HSP72,HSP25表达,在慢性心理应激中对工作记忆具有保护作用。
Objective To investigate the potential involvement of HSF1 and HSP in protection of working memory during chronic psychological stress. Methods HSF1 +/+ and HSF1-/- mice were submitted to chronic psychological stress and heat shock pretreatment plus psychological stress for 2 month. Working memory of mice were assessed using T maze, expression of HSP72, HSP25 was detected by western blots. One way ANOVA and 3-way ANOVA were used to analysis the correct alternations in T maze and HSP expression of mice in each group. Results Chronic psychological stress didnt decrease correct alternations in T maze of HSF1 + / + mice (8.90 ± 0.46) than control mice (9.58 ± 0.48 ), F±,65) = O. 23, P 〉 0.05 ), but decreased correct alternations in T maze in HSF1-/- mice (4.00 ±0.26) than control mice(7.33 s0.43, F/1.65) =32.39, P〈0.05). HSF1 knock out mice abolished inducible expression of HSP72 (0.23 ± 0.03 ) and HSP25 (0.26 ± 0.02 ) in HSF1-/- mice than HSF1 + / + mice ( 1.35 ± 0.11,1.05 ± 0.03, all P 〈 0.05 ) during psychological stress. Heat shock pretreatment induced HSP72 ( 1.71 ± 0.05 ), HSP25 ( 1.33 ± 0.05 ) expression were higher in HSF1 + / + mice than in HSF1-/- mice (0.26 ± 0.03, 0.23 ± 0.08, all P 〈 0.05 ), but failed to find a main effect of heat shock pretreat- ment on correct alternations of mice in T maze during psychological stress( F (1.65) = 0.32, P 〉 0.05 ). Conclu- sion HSF1 and HSP72, HSP25 induced by psychological stress play an important role in protection of working memory during chronic psychological stress.