氟西汀对抑郁障碍大鼠海马区域FGF-2、FGFR1及5-HT1AR表达的影响

Effects of fluoxetine on the expression of FGF-2,FGFR1 and 5-HT1AR in the hippocampus of depression model rats

目的通过建立慢性不可预知的温和刺激建立大鼠抑郁症模型,来观察氟西汀对抑郁障碍大鼠海马区域成纤维细胞生长因子-2(fibroblast growth factor-2,FGF-2)、成纤维细胞生长因子受体1(fibroblast growth factor receptor1,FGFR1)和5-羟色胺1A受体(5-hydroxytryptamine 1A receptor,5-HT1AR)表达的影响。方法利用敞箱实验进行行为学评分,选择得分相近的SD健康雄性大鼠32只,体重210~290 g。利用随机数字表法随机分为4组,每组8只,包括(1)抑郁模型组;(2)抑郁模型+氟西汀组;(3)空白对照组;(4)氟西汀组。采用慢性不可预知的温和刺激建立大鼠抑郁症模型,应激同时抑郁模型+氟西汀组、氟西汀组予氟西汀[5 mg/(kg·d)]灌胃,空白对照组、抑郁模型组每日给予等体积0.5%的羧甲基纤维素纳悬浮液灌胃处理,共21 d。21 d后,采用敞箱实验、糖水消耗实验指标评定大鼠行为学改变并检测模型是否成功建立。应用Western blot法检测各组大鼠海马区域的FGF-2、FGFR1和5-HT1AR蛋白表达水平,统计学分析采用单因素方差分析。结果 (1)敞箱实验、糖水消耗实验显示抑郁模型建立成功。与模型组比较,模型+氟西汀组水平和垂直得分增高,排便粒数减少,糖水消耗增加(P<0.05)。(2)与空白对照组比较,抑郁模型组SD大鼠海马FGF-2(22.21±7.23)、FGFR1(20.51±6.67)、5-HT1AR(22.61±5.49)蛋白表达显著下降(P<0.05);而氟西汀组无明显差异(P>0.05)。与抑郁模型组比较,抑郁模型+氟西汀组FGF-2(42.44±8.01)、FGFR1(42.50±9.30)、5-HT1AR(50.97±6.24)蛋白表达显著升高,差异有统计学意义(均P<0.05)。结论氟西汀可改善抑郁障碍大鼠的抑郁行为,其病理生理作用机制可能是与FGF-2、FGFR1、5-HT1AR在大鼠海马中的表达上调相关。

Objective To investigate the effect of fluoxetine on the expression of fibroblast growth factor-2, fibroblast growth factor receptor 1 and 5-hydroxytryptamine （ 5-HT ） 1A receptor in the hippocampus of depression model rats. Methods The behavior scores was evaluated by using open-field test. Forty heahhy male SD rats weighting 210 to 290 g with the similar score were selected and randomly divided into 4 groups （8 in each group） based on the random number table, including chronic unpredictable mild stress（CUMS） group, CUMS plus fluoxetine group, control group and flnoxe- tine group. Chronic mild unpredicted stress was taken to establish rat depression model for 21 days. The iluoxetine group and CUMS plus fluoxetine group were treated with intragastric administration of flnoxetine [ 5 mg/（ kg ·d） ], meanwhile the control group and CUMS group were treated with 0.5% carboxymethyl cellulose sodium in the same way. The openfield test and sucrose consumption were used to evaluate the depression behaviors of rats. And the expression of FGF-2, FGFR1 and 5-HT1AR in the hippocampus of rats were detected by western blot. Results （1）The open-field test and sucrose consumption showed that the rat model of depression has been established successfully. Compared with the CUMS group, the sucrose consumption, crossing score and rearing score in the CUMS plus fluoxetine group were significantly increased, while the number of defecate was significantly decreased （all P 〈0. 05 ）. （2）Compared with control group, the level of FGF-2, FGFR1 and 5-HT1AR in hippocampus of rats were significantly decreased in CUMS group （ P 〈 0.05 ）, while fluoxetine group showed no significant difference（ P 〉 0. 05 ）. The expression of FGF-2, FGFR1 and 5-HT1AR in hippocampus of the CUMS plus fluoxetine group were significantly higher than the CUMS group （ allP 〈 0.05 ）. Conclusion Fluoxetine can be used to improve depressive behaviors, which maybe associate with the increased expression level of FGF-2, FGFRl and 5-HT1AR protein in rat hippocampus.