盐酸氟西汀对抑郁症模型小鼠神经肽Y表达的研究

The effect of fluoxetine hydrochloride in expression of neuropeptide Y of hypothalamus in depression mice model under chronic stress

目的探讨盐酸氟西汀对慢性应激抑郁症模型小鼠下丘脑神经肽Y(NPY)的表达影响。方法采用旷场试验(Open-Field)法,比较抑郁症模型小鼠与正常对照组行为学改变方面的差异。将慢性应激抑郁症小鼠模型随机分成盐酸氟西汀和阿米替林治疗组、模型对照组,同时设立空白对照组,利用半定量逆转录-聚合酶联反应(RT-PCR)法、细胞酶联免疫法和蛋白免疫印迹(Western-blot)技术,比较试验组小鼠下丘脑NPY的表达变化。结果(1)与正常组比较,模型组在总路程缩短、活动次数减少和体重增加幅度下降等方面具有显著性差异。(2)与正常组比较,抑郁症模型组下丘脑NPY的mRNA表达下降。(3)经过3周的治疗,盐酸氟西汀组和阿米替林组小鼠下丘脑NPY的mRNA及蛋白表达没有明显差别,但是两组的表达结果显著高于模型对照组,与空白对照组的结果接近。结论脑内NPY的mRNA及蛋白的表达增加可能是盐酸氟西汀治疗抑郁症小鼠的机制之一。

Objective To study the influence of fluoxetine hydrochloride in neuropeptide Y （NPY） expression in depression mice model under chronic stress. Methods Differences of behavior changes were investigated by open-field method between depression mice and normal controls. Levels of both mRNA and protein expression of hypothalamus NPY were detected by using the techniques of semi-quantitative （RT-PCR）, cellular immunoassay and Western-blot in random groups of depression mice treated with fluoxetine hydrochloride and amitriptyline, respectively, compared with sham controls and black controls. Results （1） Compared to black controls, the decrease of total distance, the activity times and the less increase of the body weight were significantly presented in depression mice; （2） the mRNA expression of the hypothalamus NPY was great lower in depression mice than in black controls; （3） There was no difference between the two drugs in term of the changes of mRNA and protein expression which were close to the level of black controls. Compared with depression mice, however, a significant increase of mRNA expression and protein content of NPY was founded in the both groups after three weeks treatment with fluoxetine hydrochloride or amitriptyline. Conclusion Taking together these data suggest that the increase of the mRNA expression and protein content of hypothalamus NPY may serve as one of therapeutic mechanisms of fluoxetine hydrochloride in the treatment of the depression mice.