舍曲林对急性应激大鼠认知功能和海马神经元GABA受体的影响

Effects of sertraline on cognitive function and GABA receptor ofhippocampus neuron in acute stress rats

目的 探讨舍曲林对急性应激大鼠认知功能及海马神经元γ-氨基丁酸能受体的影响.方法 通过迷津试验筛选出认知功能差异无显著性的雄性SD大鼠24只,随机分成对照组、模型组、舍曲林A组、舍曲林B组,每组6只.除对照组不做处理外,其他各组于造模前腹腔内分别注射双蒸水、舍曲林5 mg·kg^-1、舍曲林10 mg·kg^-1作预处理,通过强迫游泳建立急性应激抑郁模型,测查各组大鼠在强迫游泳中的不动时间及其游泳后迷宫中的潜伏期;采用免疫组化法,观察各组大鼠海马CA1、CA3区及DG门区γ-氨基丁酸免疫阳性细胞数的变化.结果 大鼠游泳中不动时间舍曲林A组及舍曲林B组均较模型组显著缩短（P＜0.01）;在迷宫中潜伏期模型组及舍曲林A组较对照组明显延长（P＜0.01）,舍曲林A组及舍曲林B组均较模型组显著缩短（P＜0.01）,舍曲林B组较舍曲林A组显著缩短（P＜0.01）.模型组大鼠海马CA1、CA3区的γ-氨基丁酸A（α）、γ-氨基丁酸B免疫阳性细胞数较对照组明显减少（P＜0.01）.舍曲林A组与舍曲林B组各区γ-氨基丁酸A（α）、γ-氨基丁酸B免疫阳性细胞数显著高于模型组（P＜0.01）;舍曲林B组γ-氨基丁酸免疫阳性细胞数较舍曲林A组增多（P＜0.01）.结论 舍曲林具有改善急性应激大鼠学习记忆功能及抗抑郁的作用,其机制可能是通过增强海马γ-氨基丁酸A（α）和γ-氨基丁酸B阳性细胞数发挥作用.

Objective To explore the effects of sertraline on cognitive function and GABA receptor of hippocampus neuron in acute stress rats. Methods Twenty-four male Sprague-Dawley （SD） rats without sig nificant cognitive differences selected through Y-maze were assigned to four groups of 6 rats each i. e. control, model, sertraline A and B group. Except control group, other 3 groups were pretreatecl with intraperitoneal injection of double-distilled water, 5mg/kg sertraline or 10mg/kg before modeling, acute stress depression model was established through forced swimming, time of immobility during forced-swimming test and latency in the maze were measured; changes of number of GABA-like immunoreactive neurons in hippocampus CA1, CA3 area and DG gate region were observed with immunohistochemisty. Results Compared with model group, immobility time shortened more significantly in both sertraline A and B groups （P〈0.01）; latency prolonged more significantly in both model and sertraline A than in control group （P〈0.01）, that shortened more significantly in both sertraline A and B than in model group （P〈 0.01）, so did in sertraline B than in A （P〈0.01）. The positive cell populations of CA1 and CA3 region a in the model group were significantly reduced compared with the control group （P〈0.01）. GABAA（a） and GABAB immunoreactive neurons in hippocampus CA1, CA3 area were significantly lower in model than in control group （P^0.01）. GABAA（a） and GABAB immunoreactive neurons were significantly-higher in both sertraline A and B than in model group（P〈0.01）; GABAB immunoreactive neurons were significantly higher in sertraline B than in A group（P〈0.01）. Conclusion Sertraline could improve learning memory function, has antidepressive action and its action mechanism may be that it produces a marked effect via strengthening GABAA（a） and GABAB immunoreactive neurons in rats.