白藜芦醇对围绝经期抑郁症模型小鼠行为及Wnt/β-catenin信号通路主要蛋白表达的影响

The effects of resveratrol on the of behavior and protein expression related to Wnt/β-catenin signaling pathway in mouse model of perimenopausal depression

目的:探讨白藜芦醇(RSV)对围绝经期抑郁症模型小鼠行为学影响及相关机制。方法:清洁级昆明小鼠随机分为假手术组、围绝经期抑郁症模型组、氟西汀+雌激素组(3 mg/kg+0.15 mg/kg)、白藜芦醇低、中、高剂量组(10、20、40 mg/kg),每组10只。采用小鼠卵巢切除(OVX)联合慢性不可预知性温和应激(CUMS)法制备围绝经期抑郁症动物模型。各给药组于每日应激前1 h灌胃给药,其余各组给予等体积生理盐水,共计21 d。采用旷场实验(OFT)、悬尾实验(TST)及体质量测试(BWM)观察小鼠行为学变化,采用Western Blot法检测脑组织Wnt_1、GSK-3β、β-catenin、CyclinD_1蛋白表达。结果:与假手术组比较,围绝经期抑郁症模型组小鼠有抑郁样行为,表现为OFT自发活动及探索行为减少、TST行为绝望时间增加、体质量测试增加缓慢(P<0.01);脑组织Wnt_1、β-catenin、CyclinD_1蛋白表达减少,GSK-3β蛋白表达增加(P<0.01)。给予不同剂量白藜芦醇治疗后,均可抑制围绝经期抑郁症模型小鼠抑郁样行为,表现为OFT自发活动及探索行为增加,TST行为绝望时间减少,体质量增加迅速(P<0.01);脑组织Wnt_1、β-catenin、CyclinD_1蛋白表达增加,GSK-3β蛋白表达减少(P<0.01);各剂量组组间比较,以中剂量较为明显(P<0.05)。结论:白藜芦醇可改善围绝经期抑郁症模型小鼠抑郁样行为,其机制与改善脑组织Wnt_1、GSK-3β、β-catenin及CyclinD_1蛋白表达有关。

Objective： To explore the effects of resveracrol on the behavior and the underlying mechanism in mouse model of perimenopansal depression. Methods： The Kunming mice were randomly devided into the sham group, the mod- el group,the fluovetine and Estrogen group （3 mg/kg ＋0.15 mg/kg） and the resveratrol group （10, 20, 40 mg/kg） ,10 mice in each group. The perimenopansal depression model in mice was established by ovariectomy and chronic unpredict- able mild stress（CUMS）. Animals for drus treatment received daily drug via gavage 1 h before stress induction. 21 days; others received equal amoant of saline with the sawe regimen. The depressed behavior of mice were obseved by open field test （OFF）, tail suspension test （TST） and body weight measurement （BWM）, the protein expression of Wntl, GSK-3beta, beta-catenin and CyclinD in brain were detected by Western Blot. Results： Compared with the sham group, the model group mice exhibited depression, showing decreased spontaneoas activity and exploring beharior, slower body weight-gcining and prolonged period of despair （P 〈 0.01 ） ; the protein expression of WntI , β-catenin and CyclinD1 in brain tissue were decreased and GSK-313 were increased （P 〈 0.01 ）. However, compared with the model group, after given different doses of resveratrol, perimenopausal depression in model mice was improved, characterized by rapid body mass increase, increased spontaneous activity and exploratory behavior of oFr and reduced despair time of TST （P 〈 0.01 ） ; the protein expression of Wnh , β-catenin and CyclinD~ in brain tissue were increased and GSK-3beta were decreased （P 〈 0. 01 ）. Compared between dose groups, medium dose yielded more obvious effects （ P 〈 0. 05 ）. Conclusion： The phytoestrogens resveratrol can improve depressive-behavior in mouse model of perimenopausal depression, and its mechanism was associated with protein expression in brain tissue of Wnt1 , GSK-3beta, beta- catenin and CyclinD1.