基于雌激素受体通路探讨青娥丸对CUMS大鼠的抗抑郁机制

目的:研究青娥丸对慢性温和不可预知应激模型(CUMS)大鼠的抗抑郁效果,及其对雌激素受体及相关信号通路的调控作用,探讨青娥丸的抗抑郁机制。方法:54只SD大鼠建立CUMS抑郁大鼠模型,实验设为正常组、模型组、草酸依他普伦组(6.3 mg·kg^-1)及青娥丸低、中、高剂量组(1.71,5.13,15.39 g·kg^-1)。CUMS造模4周后给予各组相应药物治疗2周,采用行为学糖水消耗实验(SPT),强迫游泳实验(FST),旷场实验(OFT)]评价大鼠抑郁状态;采用蛋白免疫印迹法(Western blot)检测雌激素受体α(ERα),雌激素受体β(ERβ),脑源性神经营养因子(BDNF)及酪氨酸激酶受体B(Trk B)的蛋白表达水平。结果:与正常组比较,模型组大鼠的糖水消耗率及旷场得分均下降(P<0.05,P<0.01),游泳不动时间显著延长(P<0.01),同时ERα,ERβ,BDNF和Trk B的蛋白表达水平下降(P<0.05,P<0.01);与模型组比较,各给药组大鼠的行为学表现得到改善,糖水消耗率及旷场得分增加(P<0.05,P<0.01),游泳不动时间减少(P<0.05),同时ERα,ERβ,BDNF和Trk B蛋白的表达明显上调(P<0.05,P<0.01),其中青娥丸中剂量组的调节作用更为显著。结论:青娥丸可改善CUMS模型大鼠的抑郁样行为,其机制可能与上调ERα,ERβ的表达,激活雌激素受体介导的ERβ/BDNF/Trk B通路起到神经保护作用有关。

Anti-depressant Mechanism of Qing'ewan in CUMS Rats Based on Estrogen Receptor Pathway

Objective:To study the anti-depressive effect of Qing’ewan in treating chronic unpredictable mild stress(CUMS)in rats,and the regulatory effect on estrogen receptor and estrogen receptor-related signaling pathways,in order to explore its anti-depressive mechanism.Method:The CUMS model was established.The experiment was divided into normal control group,model group,escitalopram oxalate group(positive control)and Qing’ewan groups(1.71,5.13,15.39 g·kg^-1).After 4 weeks of modeling,rats were treated with corresponding drugs for 2 weeks.Behavioral evaluationsucrose preference test(SPT),forced swimming test(FST),open field test(OFT)]was conducted to assess if the CUMS model was successful.Western blot was used to analyze the protein expression levels of estrogen receptorα(ERα),estrogen receptorβ(ERβ),brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB).Result:Compared with the normal group,the sucrose consumption rate and the score of OFT in the model group decreased(P<0.05,P<0.01),the immobility time of FST prolonged significantly(P<0.01),and the protein expression levels of ERα,ERβ,BDNF and Trk B decreased(P<0.05,P<0.01).Compared with the model group,the behavioral performance of the treated group was improved,the sucrose consumption rate and the score of OFT increased(P<0.05,P<0.01),and the immobility time decreased(P<0.05).The protein expressions of ERα,ERβ,BDNF and TrkB in the treated group were significantly up-regulated(P<0.05,P<0.01),especially the middle-dose Qing’ewan group(5.13 g·kg^-1).Conclusion:Qing’ewan can improve depression-like behavior in CUMS rats.Its mechanism may be related to the neuroprotective effect by up-regulating the expressions of ERαand ERβand activating estrogen receptor-mediated ERβ/BDNF/TrkB pathways.