目的 探索海马Wnt/β-catenin信号通路的改变在产前应激(PS)子代大鼠抑郁和焦虑样行为中的作用.方法 通过大鼠产前束缚应激建立抑郁模型,将体质量240～260 g的Sprague-Dawley雌鼠随机分成2组,对照组于孕期不做任何处理,产前束缚应激组于孕14～20 d给予束缚应激,3次/d,45 min/次.1月龄子代大鼠随机分为2组:对照组和产前应激组进行实验研究.采用旷场实验(OFT)和强迫游泳实验(FST)评价各组大鼠的抑郁和焦虑样行为,通过Western blot测定各组大鼠海马区Wnt1、Gsk-3β,β-catenin蛋白的表达.结果 与对照组相比,产前应激组子代大鼠在旷场实验中的穿越中央格次数明显减少(P＜0.01),中央格停留时间显著减少(P＜0.05),在强迫游泳实验中不动时间明显延长(P＜0.01),表现出明显的焦虑和抑郁样行为.PS使大鼠子代海马Gsk-3β表达显著增加(P＜0.01),使β-catenin和Wnt1表达明显降低(P＜0.01).结论 产前应激导致Wnt/β-catenin信号系统功能改变,可能引起子代大鼠抑郁和焦虑样行为的产生.%Objective To explore the pathogenic role of changes of Wnt/β-catenin signaling pathway in the hippocampus in depression-and anxiety-like behaviors caused by prenatal stress (PS) in offspring rats.Methods Twelve female SpragueDawley rats weighing 240-260 g were randomly divided into control and restraint stress groups.The rats in the control group received no interventions, and those in restraint stress group were subjected to restraint stress (three times a day, 45 min each time) at the gestational age of 14-20 days.The 1-month-old offspring rats underwent open field test and forced swimming test to assess the anxiety-and depression-like behaviors, and the expressions of Wnt1, Gsk-3β and β-catenin in the hippocampus were detected using Western blotting.Results In open field test, the offspring rats with PS showed significantly decreased crossings of the center (P＜0.01) with reduced time spent in the center (P＜0.05) compared with control offspring rats.In forced swimming test, the offspring rats in PS group exhibited a significantly longer immobility time than in the control rats, and showed obvious depression-and anxiety-like behaviors.Compared with those in the control offspring rats, Gsk-3β expression increased significantly while the expressions of β-catenin and Wnt1 were significantly lowered in the hippocampus of the offspring rats in PS group (P＜0.01).Conclusion PS causes changes in Wnt/β-catenin signaling pathway in the hippocampus to contribute to the occurrence of depression-and anxiety-like behaviors in rats.
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