Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E2/ERβ Signaling Pathway
10.13422/j.cnki.syfjx.20211903
- VernacularTitle:E2/ERβ信号通路介导引火汤改善慢性应激诱导的双侧卵巢摘除小鼠抑郁样行为
- Author:
Hong-dan XU
1
;
Qi QIU
2
;
Yan-qiu DU
2
;
Shuang LIU
2
;
Shu-ming HUANG
3
Author Information
1. College of Jiamusi，Heilongjiang University of Traditional Chinese Medicine（TCM），Jiamusi 154007，China
2. School of Pharmacy，Heilongjiang University of TCM，Harbin 150040，China
3. Institute of Traditional Chinese Medicine，Heilongjiang University of TCM，Harbin 150040，China
- Publication Type:Research Article
- Keywords:
Yinhuotang （YHT）;
depression;
estradiol （E2）;
estrogen receptor α （ERα）;
estrogen receptor β （ERβ）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(21):10-18
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of Yinhuotang （YHT） on the depression-like behavior of mice with bilateral ovariectomy （OVX） induced by chronic stress and explore its action mechanism based on estradiol （E2）-estrogen receptor β （ERβ） pathway. Method:The experiment was divided into two parts. In the first part， mice were randomly divided into the sham operation （Sham） group， model （OVX） group， positive drug （E2， 0.13 mg·kg-1） group， and YHT （23.4 g·kg-1） group. The OVX model was reproduced by OVX combined with chronic unpredictable mild stress （CUMS）. On the 8th day after OVX， the mice in each group were exposed to CUMS and treated with drugs. The changes in immobility time， horizontal movement score， and vertical movement score of mice in each group were observed in forced swimming test （FST）， tail suspension test （TST） and open-field test （OFT）， respectively. Serum and brain E2 levels were detected by enzyme-linked immunosorbent assay （ELISA）， the aromatizing enzyme （Cyp19） mRNA expression by real-time fluorescence polymerase chain reaction （Real-time PCR）， the expression of ERα and ERβ in dentate gyrus of hippocampus by immunohistochemistry （IHC）， and the total ERα and ERβ levels in the brain by Western blotting. In the second part， the mice were divided into the Sham group， OVX group， YHT group， and blocker （Y+B， 23.4 g·kg-1+100 μg·kg-1） group. Mice in the Y+B group were first treated with intragastric administration of YHT and then with intraperitoneal injection of ERβ blocker （PHTPP） on the next day. The changes in immobility time， horizontal motor score， and vertical motor score were observed in the three behavioral tests. Result:Compared with the Sham group， the OVX group displayed significantly increased immobility time， decreased horizontal and vertical movement scores （P<0.01）， down-regulated serum and brain E2 levels （P<0.01） and Cyp19 mRNA expression in the brain （P<0.01）， and up-regulated total ERβ in dentate gyrus and brain （P<0.01）. However， there was no significant change in total ERα expression in the dentate gyrus or brain. As revealed by comparison with the OVX group， the immobility time of the E2 group was decreased significantly， while the horizontal and vertical movement scores were increased significantly （P<0.01）. The E2 levels in the serum was significantly elevated （P<0.01）. The Cyp19 mRNA expression in the brain and the total ERα expression in the dentate gyrus and brain were not significantly changed， while the expression levels of total ERβ in dentate gyrus and brain were significantly increased （P<0.01）. In the YHT group， the immobility time declined significantly， and the horizontal and vertical movement scores rose significantly （P<0.01）. The serum E2 did not increase， whereas the brain E2 increased significantly （P<0.01）. The expression of Cyp19 gene in the brain was significantly increased （P<0.05，P<0.01）. There was no significant change in the total ERα of dentate gyrus and brain， but the expression levels of total ERβ in dentate gyrus and brain were significantly increased （P<0.05，P<0.01）. PHTPP reversed the effects of YHT on OVX mice in FST， TST and OFT. Conclusion:YHT promotes the synthesis and release of endogenous estrogen in brain and improves the depression-like behavior of OVX mice induced by chronic stress， which is possibly related to the activation of E2/ERβ pathway.
