Effects of Jiawei Baihe Dihuang Decoction on HPO axis and estrogen receptor expression in perimenopausal depression model rats
Objective To explore the efficacy and potential mechanism of Jiawei Baihe Dihuang Decoction(JWBHDHD)in treating perimenopausal depression based on the hypothalamic-pituitary-ovarian axis(HPO axis)and estrogen receptor(ER).Methods The rats were randomized into normal control group,model group,positive drug group(1.89 mg/kg of flupentixol-melitracen solution),and high-,medium-,and low-JWBHDHD doses(16.2,8.1,4.05 g/kg)groups,with 10 rats in each group.Except the normal control group,all the other groups were established a perimenopausal depression rat model by bilateral ovariectomization combined with chronic unpredictable stress.After 21 days of administration in each group,a sugar preference test and a forced swimming test were used to evaluate the depression-like behavior of rats;enzyme-linked immunosorbent assay was used to check serum gonadotropin-releasing hormone(GnRH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E2)levels;HE staining was used to observe the histopathological damage of the hypothalamus,pituitary gland,and hippocampus;the expressions of estrogen receptor genes and proteins in the hypothalamus and hippocampus tissues were detected by RT-PCR and Western blot.Results Compared with the normal group,the preference for sugar water of rats in the model group significantly decreased(P<0.01),the immobility time of forced swimming significantly increased(P<0.01),and the rats in the model group showed obvious depression-like behaviors,the content of serum GnRH,FSH,and LH was significantly higher(P<0.01 or P<0.05),and E2 was lower(P<0.01).The hypothalamus,pituitary,and hippocampal tissues were damaged,and the expression of estrogen receptors was significantly lower(P<0.01).After the intervention of JWBHDHD,the depression-like behavior of model rats was significantly improved(P<0.01 or P<0.05),the hyperactivity of HPO axis and hippocampal injury were relieved,and the expression of estrogen receptor in hypothalamus and hippocampal significantly increased(P<0.01 or P<0.05).Compared with the positive drug group,the expression of estrogen receptor genes in the hypothalamus of the high-dose JWBHDHD group significantly increased(P<0.05).Conclusion JWBHDHD exerts an anti-perimenopausal depression role by inhibiting HPO axis hyperactivity and increasing estrogen receptor levels in the brain.
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