鼠尾悬吊法小鼠抑郁模型的评价及其对下丘脑-腺垂体-甲状腺轴的影响

Evaluation of a mouse depression model induced by tail-suspension and its effect on the function of hypothalamus-pitnitary-thyroid axis

目的通过鼠尾悬吊法建立小鼠的抑郁模型并对其进行评价,研究该模型对下丘脑-腺垂体-甲状腺轴(HPT轴)的影响。方法健康昆明小鼠30只,按照随机数字表法分为空白对照组、悬吊14 d组、悬吊28d组,每组雌、雄各5只,28d后采用强迫游泳实验研究小鼠行为学表现,留取甲状腺、垂体、下丘脑组织及股动脉血,采用ELISA法测定下丘脑5-羟色胺(5-HT)和去甲肾上腺素(NE)水平,采用紫外分光光度法测定下丘脑单胺氧化酶(NAO)活力,采用化学发光免疫分析法检测血清FL、FT4,采用ELISA法检测血清促甲状腺激素(TSH)水平,HE染色观察甲状腺形态学变化,三色染色观察垂体形态学变化。结果与空白对照组相比,悬吊14d组和悬吊28 d组强迫游泳实验累计不动时间均增加(F=9.393,P<0.01),下丘脑5-HT和NE水平、血清FT4水平均降低(F=3.498、5.773、9.096,P均<0.05)。与空白对照组相比,悬吊28 d组下丘脑MAO活力升高(F=3.498,P<0.05),甲状腺滤泡大小不均,滤泡上皮扁平。结论鼠尾悬吊法建立小鼠的抑郁模型有效,此干预使小鼠HPT轴功能减低,但尚可通过增加T4向L的转化而代偿。

Objective To establish and evaluate a mouse model of depression induced by tail-suspension and to explore its effect on the function of hypothalamus-pituitary-thyroid axis(HPT axis).Methods Thirty healthy Kunming mice were randomly divided into three groups according to random number table method:control group,14-day tail-suspended group and 28-day tail-suspended group,with 5 females and 5 males in each group.Twenty-eight days later,forced swimming test were applied to evaluate the depressive behavior of mice;then thyroid,pituitary,hypothalamus tissue and blood from femoral artery were harvested. The level of 5-hydroxytryptamine (5-HT)and norcpinephrine (NE)in hypothalamus were detected by ELISA,the activity of monoamine oxidase (MAO)in hypothalamus was detected by uhraviolet spectrophotometry,serum FT3 and FT4 level were detected by chemiluminescence,and thyroid stimulating hormone (TSH)in serum was detected by ELISA.Morphological changes of the thyroid stained with HE and pituitary stained with Mallory were observed.Results Compared with control group,the total immobility time in the forced swimming test was significant longer(F =9.393,P <0.01 )in the forced swimming test,the levels of hypothalamus 5-HT and NE as well as serum FT4 were significant lower (F =3.498,5.773,9.096,all P <0.05)in 14-day tail-suspended group and 28-day tail-suspended group.Compared with control group, the activity of MAO in hypothalamus was significant higher in 28-day tail-suspended group (F =3.498, P <0.05 ).Moreover,the thyroid follicles were not uniform in size and the follicular epithelium was fiat in 28-day tail-suspended group.Conclusion It is effective to establish a depressive mouse model induced by tail-suspension and the function of HPT axis in this model is inhibited,but can be compensated by conversion more T4 to T3.