慢性应激大鼠中枢5-羟色胺含量及色氨酸羟化酶-2的表达变化

目的 探讨慢性不可预知轻度刺激（CUMS）大鼠模型中枢5-羟色胺（5-HT）含量和色氨酸羟化酶-2（TPH-2）的表达变化以及抗抑郁药的影响.方法 24只大鼠被随机分成3组,每组8只,A组为对照组,不给予刺激;B组为刺激不给药组,即CUMS应激鼠;C组为刺激给药组,即CUMS应激＋西酞普兰治疗组.实验为期6周,每周为大鼠称重,每3周测大鼠的糖水偏爱性,造模前后通过旷场试验评价大鼠行为,6周后对大鼠进行处死.处死后脑组织取样测定各脑区5-HT浓度及TPH-2 mRNA的表达水平.结果 经过6周干预,与A组比较,B组和C组体重明显降低（P＜0.05）;与A组及C组比较,B组糖水偏爱度显著降低（P＜0.05）,同时行为增多;B组5-HT浓度在海马中高于A组和C组,差异有统计学意义（P＜0.05）;在纹状体中,B组和C组5-HT浓度低于A组,差异有统计学意义（P＜0.05）;B组大鼠TPH2 mRNA在中缝核中表达低于A组,差异有统计学意义（P＜0.05）.结论 慢性应激可能引起中枢海马5-HT浓度增高及中缝核TPH-2表达降低,抗抑郁药可能引起中枢海马5-HT浓度降低,但未能影响中枢TPH-2的表达.

Expression of TPH-2 and content of 5-HT in the brain of rats with chronic unpredictable mild stress

Objective To investigate the expression of TPH-2 and the content of 5-HT in different areas of the brain in rats with chronic unpredictable mild stress （CUMS）,and explore the effects of antidepressant on expression of TPH-2 and content of 5-HT.Methods Twenty-four male SD rats were randomly assigned to control group （group A）,CUMS group （group B）,and CUMS＋ citalpram group （group C） with 8 rats in each group.The experiment lasted for 6 weeks.Body weight was measured each week,sugar preference was evaluated every 3 weeks,and behavior of rats was assessed through open field tests before model establishment and 6 weeks after model establishment.Animals were sacrificed after 6 weeks,brain tissues were obtained,and the expression of TPH-2 mRNA and the content of 5-HT in different areas of brain detected.Results After the beginning of stress experiment,the body weight of rats in group B and group C was significantly lower than that in group A （P ＜0.05）.Rats in group B has significantly lower sugar preference than group A and group C （P ＜ 0.05）,and had higher activity.The content of 5-HT in hippocampus of rats in group B was higher than that in group A and group C,while there was significant difference between them （P ＜ 0.05）,The content of 5 -HT in striatum of rats in group B and group C was lower than that in group A （P ＜ 0.05）.The expression of TPH-2 mRNA in raphe nuclei of rats in group B was lower than that in group A （P ＜0.05）.Conclusions Chronic stress may increase the content of 5-HT in hippocampus and decrease the expression of TPH-2 in raphe nuclei,while antidepressant may decrease the content of 5-HT in hippocampus without affecting the expression of TPH-2.