慢性强迫游泳应激对大鼠海马神经元再生和p-CREB表达的影响

The effects of repeatedly forced swim stress on hippocampal neurogenesis and p-CREB expression in rats

目的 研究慢性强迫游泳应激模型大鼠海马神经元再生和磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）的表达.方法 30只雄性SD大鼠随机分为3组：强迫游泳7 d组（S1组）、强迫游泳14 d组（S2组）和对照组.S1组和S2组分别连续强迫游泳7 d和14 d,每天5 min,水温（10±0.5）℃.采用免疫组化半定量测定大鼠海马5-溴脱氧尿苷（BrdU）和p-CREB阳性细胞表达情况.结果 免疫组化结果 显示,在整个海马结构中BrdU及p-CREB的阳性细胞主要集中于齿状回的颗粒细胞下层.与对照组比较,S1组、S2组大鼠海马齿状回BrdU和p-CREB阳性细胞数均明显减少（P＜0.01）;而与S1组比较,BrdU阳性细胞数无统计学差异（P＞0.05）,S2组p-CREB阳性细胞数进一步减少（P＜0.01）.结论 慢性强迫游泳应激可导致海马神经元再生功能障碍,其机制可能与p-CREB信号转导通路有关. 基金项目：

Objective The aim of this study was to explore stress--induce effect on hippocampal neurogenesis and p--CREB expression following rePeatedly forced swim stress in rats. Methods Thirty male SD rats were randomly divided into 3 groups： the control group and the stress groups （Stress-1 and Stress-2）. Rats in stress groups were administered to repeatedly forced swim 7 or 14 days respectively. The expression of BrdU and p-CREB positive cells in dentate gyrus of hippocampus was detected with immunohistochemistry and analyzed by image analysis system. Results Results of immunohistochemistry showed the BrdU and p-CREB positive cells in hippocampus relatively concentrated in the subgranular zone of dentate gyrus. The BrdU and p-CREB positive cells in dentate gyrus of S1 and S2 groups significantly decreased compared to Control group （P 〈 0.01）. Compared to S1 group, no significant difference was found about BrdU positive cells in S2 group （P 〉 0.05）, but p-CREB positive cells significant decreased in S2 group （P 〈 0.01）. Conclusions Repeatedly forced swim stress in rats inhibited hippoeampal neurogenesis, which may associate with the disregulation of p-CREB protein expression.