氟西汀对慢性不可预知性轻度应激抑郁模型大鼠下丘脑—垂体—肾上腺轴的影响

Effect of fluoxetine on hypothalamic-pituitary-adrenal axis in ratwith chronic unpredictable mild stress depression

目的观察氟西汀对慢性不可预知性轻度应激(CUMS)抑郁模型大鼠5-羟色胺(5-HT)、下丘脑—垂体—肾上腺(HPA)轴以及海马区神经因子受体5-羟色胺受体3A(HTR3A)、促皮质素释放激素受体1(CRHR1)、CRHR2和糖皮质激素受体(GR)表达的调节,探讨氟西汀通过5-HT系统对HPA轴的影响。方法健康SD雄性大鼠18只,随机分为正常对照组、抑郁模型组、盐酸氟西汀组。抑郁模型组和盐酸氟西汀组大鼠采用CUMS结合孤养法制备大鼠抑郁模型。采用酶联免疫法和荧光定量PCR分析5-HT和HPA轴神经内分泌因子5-HT、促肾上腺皮质释放激素(CRH)和皮质酮(CORT)及其受体的表达。结果 CUMS大鼠5-HT降低(P<0.01),HPA轴CRH、CORT增加(P<0.01),使用氟西汀后,5-HT、CRH和CORT的含量均出现逆转。CUMS大鼠海马的HTR3A mRNA和GRmRNA表达水平下降(P<0.01),使用氟西汀后,HTR3A升高(P<0.01),但对GR无影响。CUMS大鼠的CRHR1 mRNA表达增高,使用氟西汀后CRHR1 mRNA表达下降,各组CRHR2差异无统计学意义。5-HT与CRH和CORT的含量均呈负相关。结论 5-HT和HPA轴两大系统存在相互影响,使用氟西汀不仅增加5-HT水平,也促进HPA轴神经因子的表达趋于正常,可能参与HPA轴的修复。

Objective To observe the effect of fluoxetine on the expression of 5-hydroxytryptamine（5-HT）,hypothalamic- pituitary- adrenal（HPA）,and their receptors,including 5- hydroxytryptamine receptor 3A（HTR3A）,corticotropin releasing hormone receptor 1（CRHRl）,CRHR2 and glucocorticoid receptor（GR） in hippocampus of rats with chronic unpredictable mild stress（CUMS）,and to investigate the effect of fluoxetine on HPA axis.Methods Eighteen SD rats were randomly divided into 3 groups,namely control groups,depression model group and fluoxetine group.Both the rats from depression model group and Fluxetine group were separately raised and exposed to chronic unpredictable mild stress.5-HT,CRH and CORT in serum were detected by enzyme- linked immunosorbent assay,and the relative content of their receptors,including HTR3 a,CRHR1,CRHR2 and GR in hippocampus were detected by real-time PCR.Results In CUMS rats,5-HT was decreased,while CRH and CORT were increased（P〈0.01）,which were reversed after administrated with fluoxetine.The mRNA expressions of HTR3 A and GR were decreased（P〈0.01） in hippocampus of CUMS rats,and fluoxetine could recover the level of HTR3 A mRNA but not the GR.The expression of CRHR1 mRNA was enhanced in CUMS rat,which was decreased after treating with fluoxetine.The difference in CRHR2 was not statistically significant between groups.5-HT was negatively correlated with the content of CRH and CORT respectively.Conclusion The system of 5-HT interact with HPA axis,and fluoxetine not only elevate the level of 5-HT,but also play the role of regulating HPA axis,which might be involved in the repair of HPA axis.