葛根素对围绝经期抑郁症模型小鼠的神经保护作用及机制研究

发布时间：2018-08-06 15:00

【摘要】：目的:探讨葛根素对围绝经期抑郁症模型小鼠行为影响及神经生物学机制。方法:清洁级昆明小鼠饲养1周以适应环境。旷场实验(OFT)筛选后,随机分为假手术组、围绝经期抑郁症模型组、氟西汀组(FLU,3mg/kg)、雌激素组(E,0.15 mg/kg)和葛根素组(92 mg/kg),每组10只。采用小鼠双侧卵巢切除(OVX)联合慢性不可预知性温和应激(CUMS)法建立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。观察小鼠动情周期变化,测定行为学变化,观察海马组织形态学改变,测定脑组织单胺类递质含量,测定海马组织c AMP反应元件结合蛋白(CREB)-脑源性神经营养因子(BDNF)信号通路主要蛋白表达。结果:与假手术组比较,各OVX组小鼠连续7 d内连续监测未见动情周期变化,证明去势成功;围绝经期抑郁症模型组小鼠呈现抑郁样行为,表现为自发活动及探索行为减少、行为绝望时间增加、体质量增长缓慢(P0.01或P0.05),海马神经元损伤、萎缩、数量减少、尼氏体减少及早期凋亡变化,脑组织五羟色胺(5-HT)、去甲肾上腺素(NE)及多巴胺(DA)含量减少(P0.01);海马组织CREB-1、磷酸化c AMP反应元件结合蛋白(p-CREB-1)、BDNF及酪氨酸蛋白激酶B(Trk B)蛋白表达减少(P0.01)。与围绝经期抑郁症模型组比较,给予葛根素(Pue)治疗后,可改善围绝经期抑郁症模型小鼠抑郁样行为,表现为增加自发活动及探索行为、减少行为绝望时间、体质量增加迅速(P0.01或P0.05);减轻海马组织神经元损伤及凋亡细胞,增加脑组织5-HT、NE及DA含量(P0.01),增加海马组织CREB-1、p-CREB、BDNF及Trk B蛋白表达(P0.01),差异具有统计学意义。结论:采用小鼠双侧OVX联合CUMS可成功制备围绝经期抑郁症动物模型。葛根素具有神经保护及抗围绝经期抑郁症作用,其机制主要通过减轻海马神经元损伤、抑制神经元早期凋亡、增加脑组织单胺类递质含量及上调脑组织CREB-BDNF信号通路主要蛋白表达而发挥的。
[Abstract]:Objective: to investigate the effect of puerarin on behavior and neurobiological mechanism of postmenopausal depression mice. Methods: Kunming mice of clean grade were raised for 1 week to adapt to the environment. After screening with (OFT) in open field experiment, they were randomly divided into three groups: sham operation group, peri-menopausal depression model group, fluoxetine group (FLUU 3mg / kg), estrogen group (estradiol 0.15 mg/kg) and puerarin group (92 mg/kg), with 10 rats in each group. The animal model of postmenopausal depression was established by bilateral ovariectomized mouse (OVX) combined with chronic unpredictable mild stress (CUMS). The rats in each group were given intragastric administration 1 hour before daily stress, and the other groups were given saline of the same volume for 21 days. The changes of estrus cycle, behavior, hippocampal morphology and monoamine transmitters in brain were observed. The expression of c AMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signal pathway in hippocampus was measured. Results: compared with sham-operation group, no oestrous cycle changes were observed in each OVX group for 7 days, which proved that ovariectomized mice showed depressive behavior in perimenopausal depression model group, which showed decreased spontaneous activity and exploratory behavior. Behavioral despair time increased, body mass increased slowly (P0.01 or P0.05), hippocampal neurons damaged, atrophy, number decreased, Nissl bodies decreased and early apoptosis changed. The contents of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) were decreased (P0.01), the expression of CREB-1, phosphorylated AMP response element binding protein (p-CREB-1) and B (Trk B) protein of tyrosine protein kinase decreased (P0.01). Compared with the model group of perimenopausal depression, puerarin (Pue) could improve the depressive behavior of the model mice in the perimenopausal depression model, which could increase spontaneous activity and explore behavior, and reduce the time of behavioral despair. The body mass increased rapidly (P0.01 or P0.05), the neuron injury and apoptotic cells in hippocampus were alleviated, the contents of 5-HTNE and DA in brain tissue were increased (P0.01), and the expression of BDNF and Trk B protein in hippocampal tissue was increased (P0.01). Conclusion: bilateral OVX combined with CUMS can be used to establish an animal model of postmenopausal depression. Puerarin has neuroprotective and anti-postmenopausal depression effects. The mechanism of puerarin is mainly by reducing hippocampal neuronal damage and inhibiting early apoptosis of neurons. Increase the content of monoamine transmitters in brain tissue and up-regulate the expression of the main protein of CREB-BDNF signal pathway in brain tissue.
【作者单位】：齐齐哈尔医学院医药科学研究院;黑龙江中医药大学中医药研究院;齐齐哈尔医学院附属第三医院呼吸内科;
【基金】：齐齐哈尔市科技攻关计划(SFGG-2015061)
【分类号】：R285.5;R-332

【参考文献】