柴坤解郁汤对围绝经期抑郁大鼠下丘脑-垂体-卵巢轴激素及下丘脑雌激素受体α表达的影响

Effect of Chaikun Jieyu Decoction on Hypothalamus-Pituitary-Ovarian Axis Hormones and the Expression of Estrogen Receptorαin Hypothalamus in Perimenopausal Depressive Rats

目的观察柴坤解郁汤对围绝经期抑郁大鼠应激状态的影响并探究其作用机制。方法将60只SD雌性大鼠随机分为假手术组,模型组,柴坤解郁汤低、中、高剂量组,盐酸氟西汀组,每组10只。采用去势手术联合慢性不可预知性温和刺激(chronic unpredictable mild stimulation,CUMS)复制围绝经期抑郁大鼠模型。模型复制同时,柴坤解郁汤低、中、高剂量组分别按照0.9、1.8、3.6 g/kg剂量给予柴坤解郁汤灌胃,盐酸氟西汀组按照2.33 mg/kg剂量给予盐酸氟西汀灌胃,假手术组和模型组给予等容积生理盐水灌胃,每日1次,共21 d。通过蔗糖水试验、旷场试验、强迫游泳试验观察其行为学变化,采用酶联免疫吸附试验检测血清卵泡刺激素(follicle-stimulating hormone,FSH)、黄体生成素(luteinizing hormone,LH)、雌二醇(estradiol,E_(2))水平变化,采用Western blot法和Rt-PCR法检测下丘脑雌激素受体α(estrogen receptor alpha,ERα)及其mRNA表达水平。结果柴坤解郁汤干预后,模型大鼠的蔗糖水偏好率、旷场总路程、旷场中心区域路程均显著升高(P<0.05),强迫游泳不动时间明显减少(P<0.05);大鼠血清FSH、LH水平显著降低(P<0.05),E_(2)水平显著升高(P<0.05),下丘脑ERα蛋白及mRNA表达水平均显著升高(P<0.05)。结论柴坤解郁汤可以有效预防并改善围绝经期抑郁大鼠的应激状态,其作用机制与调节下丘脑-垂体-卵巢轴激素含量和下丘脑ERα表达水平有关。

Objective To investigate the effect of Chaikun Jieyu Decoction(CKJYD)on the stress state of perimenopausal depressive rats and its mechanism of action.Methods A total of 60 female Sprague-Dawley rats were randomly divided into sham-operation group,model group,low-,middle-,and high-dose CKJYD groups,and fluoxetine hydrochloride group,with 10 rats in each group.A rat model of perimenopausal depression was established by ovariectomy combined with chronic unpredictable mild stimulation.The rats in the low-,middle-,and high-dose CKJYD groups were given CKJYD by gavage at a dose of 0.9,1.8,and 3.6 g/kg,respectively,those in the fluoxetine hydrochloride group were given fluoxetine hydrochloride by gavage at a dose of 2.33 mg/kg,and those in the sham-operation group and the model group were given an equal volume of normal saline by gavage,once a day for 21 days.Sucrose water test,open field test,and forced swimming test were used to observe behavioral changes;ELISA was used to measure the changes in the serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E_(2)),and Western blot and Rt-PCR were used to measure the expression level of estrogen receptor alpha(ERα)and its mRNA in the hypothalamus.Results After the intervention with CKJYD,the model rats had significant increases in the preference rate of sucrose water,the total distance of open field test,and the total distance of central area(P<0.05)and a significant reduction in immobility time in forced swimming test(P<0.05),as well as significant reductions in the serum levels of FSH and LH(P<0.05),a significant increase in the level of E_(2)(P<0.05),and significant increases in the protein and mRNA expression levels of ERαin the hypothalamus(P<0.05).Conclusion CKJYD can effectively prevent and improve the stress state of menopausal depressive rats,possibly by regulating the hypothalamus-pituitary-ovarian axis hormones and the expression of ERαin the hypothalamus.