雌激素对围绝经期抑郁大鼠的神经保护作用及可能机制

Neuroprotective effects of estrogen on rat model of perimenopausal depression and possible mechanism

目的探讨雌激素对围绝经期抑郁症模型大鼠行为的影响及作用机制。方法通过双侧卵巢切除加慢性温和应激建立围绝经期抑郁症大鼠模型,实验分为正常对照组、卵巢切除组、模型组(卵巢切除+慢应激)、雌激素(雌二醇,E2)治疗组、西酞普兰治疗组和卵巢切除+雌激素共6组。采用旷场和糖水偏好实验检测大鼠抑郁样行为;尼氏染色观察海马齿状回(DG)区神经元数量变化;高效液相检测海马5-HT、5-H1AA、去甲肾上腺素(NE)和多巴胺(DA)含量;酶联免疫法检测下丘脑-垂体-肾上腺(HPA)轴相关指标的含量。结果 E2治疗可逆转模型组导致的大鼠水平、垂直运动得分降低、糖水偏好率减少及海马DG区神经元数量减少;且可逆转减少的海马单胺递质和HPA轴亢进状态。结论雌激素可通过改善海马神经元损伤、增加脑组织单胺类递质含量及缓解HPA轴的亢进发挥抗围绝经期抑郁作用。

Objective To investigate the antidepressant roles of estrogen in the perimenopausal depression rat model and potential mechnisms. Methods The perimenopausal depression rat model was performed by ovariectomized（OVX）rat following unpredictable chronic mild stress（UCMS）. The rats were divided into 6 groups：the control group（CON）,OVX group,model（OVX＋UCMS）group,estrogen（estradiol,E2）treatment group,escitalopram group（ESC）,and OVX＋E2 group. Open filed and sucrose preference tests were used to investigate depression-like behavior. Nissl staining was used to analyze neuron numbers in the dentate gyrus（DG）region of rat hippocampus,Levels of 5-HT,5-H1 AA、norepinephrine（NE）and dopamine（DA）in the hippocampus were determined by the HPLC method,while the levels of several markers associated with HPA axis were determined by ELISA. Results OVX＋UCMS decreased the number of crosses and rearings in open field test and decreased sucrose preference in sucrose preference test in the perimenopausal depression rat model. E2 treatment could reverse the depression behavior. E2 treatment also reversed the decreased neuron numbers of DG region in the rat hippocampus and decreased monamine transmitter and high hypothalamic-pituitary-adrenal axis（HPA）activation. Conclusion E2 plays antidepressant roles in perimenopausal depression rat model through protecting neuron,increasing monamine transmitter level and decreasing HPA axis activation.