中文摘要：

目的采用热休克因子1（HSF1）基因敲除小鼠模型，探讨HSF1基因及热休克预处理在慢性心理应激中对小鼠探索行为的保护作用，以及其机制是否与CA1区神经元凋亡有关。方法选取HSF1基因野生型小鼠40只和HSF1基因敲除小鼠36只，均随机分为热应激组、心理应激组、热应激加心理应激组和对照组，除对照组外各组给予相应的应激措施2个月，热应激加心理应激组小鼠在暴露于慢性心理应激前给予热休克预处理。2个月后检测各组小鼠高架十字迷宫中总探索次数、简易迷津探索格数及小鼠海马CA1区神经元的凋亡。结果野生型小鼠和基因敲除小鼠中心理应激组高架十字迷宫中总探索次数、简易迷津探索格数均较对照组减少（P〈0．05）。野生型小鼠热应激加心理应激组高架十字迷宫中总探索次数、简易迷津探索格数均较心理应激组多（P〈0．05），而基因敲除小鼠中不存在这一差异（P〉0．05）。基因敲除小鼠心理应激组CA!区海马神经元凋亡数目多于对照组（P〈0．05）。在全部76只小鼠中进行分析，小鼠高架十字迷宫总探索次数、简易迷津探索总格数与CA1区神经元凋亡负相关（r=-0．50，P〈0．01；r=-0．51，P〈0．01）。结论热应激预处理通过HSF1基因，抑制慢性心理应激所致探索行为减少，热应激预处理及HSF1基因对CA1区神经元的内源性保护作用可能是维持小鼠探索行为的重要机制。

英文摘要：

Objective To investigate the effects of heat shock factor 1 （HSF1） gene and heat shock stress on explor- atory behavior and CA1 neurons during chronic psychological stress （ CPS）, and to explore the association of exploratory be- havior with the hippocampal CA1 neurons. Methods Forty HSF1 wild type mice and 36 HSFl-null mice were randomly di- vided into 4 groups： heat shock stress group, psychological stress group, and heat shock stress plus psychological stress group, non-stress group. These animals were then exposed to different stressors for 2 months. The animals in heat shock stress plus psychological stress group were pretreated with heat shock before exposed to CPS. Exploratory behaviors were assessed u- sing elevated-plus maze （EPM） and noval cage （NC）. Apoptotic CA1 neurons were detected. Results The number of arms entries in EPM and the number of holes crossed in NC were significant lower in heat shock group than in control group in both HSF1 wild type and HSFl-null mice （P 〈 0. 05）. The number of arms entries in EPM and the number of holes crossed were higher in heat shock stress plus psychological stress group than in psychological stress group in wild type mice（P 〈0. 05） but not in HSFl-null mice （P 〉 0. 05 ）. The number of apoptotic CA1 neurons in HSFl-null mice was increased in psychological stress group compared with control group. In HSFl-null mice, the number of arms entries in EPM and the number of holes crossed in NC were negatively correlated with the number of apoptotic CA1 neurons （r = -0. 50,P 〈0. O1 ;r = -0. 51 ,P 〈 0. 01）. Conclusions CPS impairs exploratory behavior, whereas heat shock pretreatment and HSF1 attenuate CPS-induced decrease of exploratory behavior. Heat shock pretreatment and HSF1 protect CA1 neurons against CPS, which may be an im- portant mechanism in maintaining exploratory behavior during CPS in mice.