反式白藜芦醇对卵巢摘除小鼠的抗抑郁作用

Antidepressant-like effect of trans-resveratrol on behavioral changes in ovariectomized mice and the possible mechanism

目的:探讨反式白藜芦醇对围绝经期抑郁模型小鼠抑郁样行为的拮抗作用及其可能机制。方法:采用去卵巢法建立围绝经期模型,再通过慢性应激建立抑郁模型。80只小鼠随机分为8组:CSV组(0.5%羧甲基纤维素钠,灌胃);COV组(0.5%羧甲基纤维素钠,灌胃);SOV组(0.5%羧甲基纤维素钠,灌胃,于每天应激前30 min给药);SOR组(反式白藜芦醇15、30、60 mg.kg-1.d-1,灌胃,于每天应激前30 min给药);SOI组(丙咪嗪10 mg.kg-1.d-1,腹腔注射,于每天应激前30 min给药);SOE组(17β-雌二醇0.1 mg.kg-1.d-1,皮下注射,于每天应激前60 min给药),每组10只。每天给药1次,连续3周。通过强迫游泳实验和开野实验观察各组小鼠的行为学改变,采用免疫组化法检测海马脑区脑源性神经营养因子(BDNF)和抗凋亡因子-2(Bcl-2)蛋白表达,检测脑内超氧化物歧化酶(SOD)活性、还原型谷胱甘肽(GSH)和丙二醛(MDA)的含量。结果:与COV组比,SOV组小鼠在强迫游泳实验中的不动时间明显延长,开野实验中水平活动和竖直活动均下降,海马脑区BDNF和Bcl-2蛋白阳性表达明显减少,脑组织中SOD活性下降,GSH含量降低,而MDA含量升高。反式白藜芦醇(30 mg.kg-1.d-1或60 mg.kg-1.d-1)能明显改善小鼠的抑郁样行为,逆转上述改变。结论:反式白藜芦醇能改善围绝经期抑郁模型小鼠的行为异常,其机制可能与其增加海马神经保护性蛋白BDNF和Bcl-2的表达及抗氧化作用有关。

Objective： To explore the antidepressant-like effects of trans-resveratrol on behavioral changes in ovariectomized mice and its possible mechanism. Methods： Sstablished were Perimenopausal model by pression model by chronic unpredictable stress were established after three weeks forced swimming test （FST） and open field test to observe the behavioral changes in of brain-derived neurotrophic factor （BDNF） and B-cell lymphoma protein 2 （Bcl-2） protein in hippocampus were determined with immunohistochemistry, the levels of superoxide dismutase （SOD）, glutathione （GSH） and malondialdehyde （MDA） were detected. Results： Compared with OVX group, the immobility time in FST and MDA level were increased, activities in open field test were decreased, BDNF and Bcl-2 expression, the activity of SOD and GSH level were reduced in OVX＋Stress group. Trans- resveratrol （30 mg·kg^-1·d^-1or 60 mg·kg^-1·d^-1） could reverse these effects mentioned above. Conclusion： Trans-resveratrol can ameliorate depressive-like behaviors in ovariectomized mice, and the mechanism may be related to its neuroprotective and antioxidant effects.