新型抗高血压复方制剂雅静胶囊降压及抗抑郁的研究

目的观察不同动物模型中新型复方制剂雅静胶囊的降压及抗抑郁作用。方法选用自发性高血压大鼠（SHR）模型、肾血管性高血压大只（RVHR）模型两种高血压动物模型,选取收缩压（SBP）、舒张压（DBP）、脉压（PP）及收缩压变异率（SBPV）4个指标观察雅静胶囊的急性降压作用。此外选用ICR小鼠通过悬尾实验和强迫游泳实验,选取不动时间和失望时间评价雅静胶囊的抗抑郁作用。结果在SHR动物模型的清醒状态下急性降压实验中,阳性药物厄贝沙坦及氢氯噻嗪组及3种不同剂量组的雅静胶囊急性给药后与给药前相比可显著降低大鼠的收缩压、舒张压．3组雅静胶囊的降压作用呈现明显的量效关系,对给药后记录8h的数据进行进一步分析提示：不同剂量雅静胶囊纽及阳性药物厄贝沙坦及氢氯噻嗪给药后0h～2h血压开始下降,在2h～4h时间段内降压效果达到最大并可维持8h．这些时间段内上述几组的SBP、DBP与对照组相比均显著下降（P〈0．05）,而PP和SBPV无统计学意义（P〉0．05）。RVHR的清醒状态下急性降压实验的结果基本类似。结论雅静胶囊能显著缩短小鼠悬尾实验的失望时间和强迫游泳实验的不动时间．提示雅静胶囊具有一定的抗抑郁作用,但该作用的量效关系不显著。     

柴胡提取组分抗抑郁作用的研究

目的 观察柴胡提取组分( CHB)的抗抑郁作用.方法 采用小鼠强迫游泳、悬尾两种“行为绝望”抑郁动物模型和利血平拮抗模型,观察CHB对小鼠游泳不动时间、悬尾不动时间以及利血平诱导的体温降低、眼睑下垂、运动不能的影响.结果 CHB 100,200 mg/kg均能不同程度地缩短小鼠强迫游泳和悬尾不动时间,能拮抗高剂量利血平致小鼠体温下降,改善利血平诱导的小鼠眼睑下垂,并呈现一定的量效关系.结论 CHB具有一定的抗抑郁作用.     

交泰丸对利血平诱导小鼠抑郁模型的影响

[目的]探讨交泰丸对利血平诱导小鼠抑郁模型的影响。[方法]采用小鼠强迫游泳实验(FST)、小鼠悬尾实验(TST)和小鼠利血平拮抗实验,通过高效液相色谱(HPLC)测定小鼠海马和皮质组织中单胺类神经递质[去甲肾上腺素(NE)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)]含量的变化,探讨交泰丸的抗抑郁作用。[结果]交泰丸组方各剂量组均能明显减少FST和TST的不动时间,并且均能拮抗利血平诱导的小鼠眼睑下垂和体温下降,而且可以逆转NE和5-HT的减少以及降低5-HIAA的含量。[结论]交泰丸具有明显的抗抑郁作用,并且可以通过调节海马组织和皮质中NE和5-HT的含量而发挥抗抑郁作用。     

L‐theanine ameliorate depressive‐like behavior in a chronic unpredictable mild stress rat model via modulating the monoamine levels in limbic–cortical–striatal–pallidal–thalamic‐circuit related brain regions

L‐theanine, originally found in green tea, elicits various physiological effects, such as promoting relaxation, improving concentration and learning ability, and providing antianxiety‐like and antidepressant‐like properties. This study aims to investigate the effects of L‐theanine (2 mg/kg) on monoamine levels in an animal model of depression. The effect of l ‐theanine on the symptoms of depression was examined through the open‐field test, sucrose preference test, and forced swim test. The monoamine neurotransmitters that involve serotonin (5‐HT), norepinephrine (NE), and dopamine (DA) were measured in the limbic–cortical–striatal–pallidal–thalamic (LCSPT)‐circuit related brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (ST), amygdala, and hippocampus (HIP). L‐theanine ameliorated the depressive‐like behaviors in the chronic unpredictable mild stress (CUMS) rat model. In the PFC, NAC, and HIP, L‐theanine administration significantly increased the levels of 5‐HT, NE, and DA. In the ST, the levels of 5‐HT and DA were increased after the administration of L‐theanine. However, in the HIP, only the level of DA significantly changed after the treatment of L‐theanine. Taken together, these results indicated that L‐theanine has possibly antidepressant‐like effects in the CUMS rat model, which could be mediated by the monoamine neurotransmitters in the LCSPT‐circuit related brain regions.     

贯郁胶囊治疗抑郁症的实验研究

目的:观察贯郁胶囊的抗抑郁作用。方法:小鼠悬尾、小鼠强迫游泳及利血平拮抗实验。结果:贯郁胶囊1. 2g kg、0. 6g kg均可显著缩短小鼠悬尾及强迫游泳不动时间(P <0 . 0 1,P <0. 0 5 ) ,并且均可显著对抗利血平所致的小鼠体温下降、眼睑下垂及运动不能(P <0. 0 1,P <0. 0 5 )。结论:贯郁胶囊具有明显的抗抑郁作用。     

青阳参总苷对慢性不可预知轻度应激大鼠的抗抑郁作用

目的:本研究评价了青阳参总苷(QYS)在慢性不可预知轻度应激(CUMS)大鼠模型上的抗抑郁活性,并通过研究其对大鼠脑内单胺神经递质浓度的影响探讨QYS的作用机制。方法:将Wistar大鼠随机分为6组,分别为正常组、模型组、氟西汀组和QYS低、中、高剂量组(0.625,2.5,10 mg·kg-1),每组9只。随机给予21 d不可预知刺激建立抑郁症模型,建模同时ig给予相应药物。造模结束后,采用旷场实验观察QYS对大鼠自主活动的影响,采用悬尾实验、强迫游泳实验观察QYS的抗抑郁作用,采用高效液相-电化学检测法测定大鼠脑内单胺递质去甲肾上腺素(NE),5-羟色胺(5-HT)及多巴胺(DA)的浓度。结果:与正常组比较,模型组大鼠悬尾时间及大鼠强迫游泳的不动时间明显延长,自主活动时间明显减少;大鼠脑内额叶皮层中NE,5-HT及DA的浓度明显降低,均具有明显的统计学差异(P0.05,P0.01);与模型组比较,QYS(0.625,2.5,10mg·kg-1)能够显著缩短模型大鼠悬尾实验中的不动时间,QYS高剂量组显著缩短模型组大鼠强迫游泳实验中的不动时间,QYS在旷场实验中对模型组大鼠的自主活动无明显影响,QYS高剂量组显著升高模型组大鼠脑内额叶皮层中NE,5-HT及DA的浓度。结论:QYS高剂量对模型抑郁大鼠具有良好的抗抑郁活性,其抗抑郁作用机制可能是QYS提高了模型大鼠脑内额叶皮层NE及5-HT水平。     

Antidepressant-like effect of ethanol extract from Paeonia lactiflora in mice

The present study investigated the antidepressant effect of ethanol extract of Paeonia lactiflora (EPL) in mice using forced swim test, tail suspension test, open-field test and reserpine test. Our results showed that intragastric administration of EPL at the doses of 250 and 500 mg/kg for seven days significantly reduced the duration of immobility in both forced swim test and tail suspension test. EPL at the dose of 500 mg/kg was as effective as the positive control (chlorimipramine, 20 mg/kg) in these tests. However, these treatments did not affect the number of crossing and rearing in the open-field test. Treating mice with EPL at the doses of 250 and 500 mg/kg significantly antagonized reserpine-induced ptosis and hypothermia. However, at the dose of 125 mg/kg, EPL antagonized only the hypothermia but not ptosis induced by reserpine. The results clearly demonstrated the antidepressant effect of Paeonia lactiflora in animal models of depression. The action of Paeonia lactiflora may be mediated via the central monoaminergic neurotransmitter system.     

Involvement of mTOR‐related signaling in antidepressant effects of Sophoraflavanone G on chronically stressed mice

SophoraflavanoneG (SG), an important prenylated flavonoid isolated from Sophoraalopecuroides.L, is effective for many illnesses. The present study was designed to investigate whether the compound could reverse depressive‐like symptoms and investigate its possible mechanisms. Chronic Unpredictable Mild Stress (CUMS) mice were treated with fluoxetine and SG. The immobility time in forced swimming test (FST) and tail suspension test (TST) were recorded. The levels of pro‐inflammatory cytokines and neurotransmitters in the hippocampus were evaluated. Furthermore, the protein expressions of PI3K, AKT, mTOR, p70S6K, BDNF, and Trkb in hippocampus were detected. Rapamycin, the selective mTOR inhibitor, was used to estimate the potential mechanism. As a result, after 7 days of SG treatment, the immobility time in FST and TST was declined obviously. The levels of IL‐6, IL‐1β, and TNF‐α in the hippocampus were significantly reduced, and the quantity of 5‐HT and NE was raised considerably in SG‐treated group compared with the CUMS‐exposed group. Additionally, SG could up‐regulate the expressions of PI3K, AKT, mTOR, 70S6K, BDNF, and Trkb. The blockade of mammalian target of rapamycin signaling blunted the antidepressant effect and reversed the up‐regulation of BDNF expression caused by SG. These findings suggested that SG treatment alleviated depressive‐like symptoms via mTOR‐mediated BDNF/Trkb signaling.     

Antidepressant evaluation of polysaccharides from a Chinese herbal medicine Banxia-houpu decoction

Banxia-houpu decoction, a traditional Chinese medicine has been used in the treatment of depression. The present study confirmed that oral administration of polysaccharides from Banxia-houpu decoction, exhibited a reduction in the immobility time in the tail suspension and in the forced swimming tests in mice in a time-dependent manner. This effect at a dose of 320 mg/kg was more potent than that at a dose of 640 mg/kg. The polysaccharides from Banxia-houpu decoction were active in animal models of depression with comparable effects to known antidepressants. The oral administration of the polysaccharides at a low dose for 4 weeks resulted in a significant increase in the monoamine neurotransmitter 5-hydroxytryptamine (5-HT) and dopamine (DA) levels in whole mouse brain, but produced no significant increase in 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) concentrations. The effect of polysaccharides on the brain neurotransmitter levels appeared to be quite different from the effect of fluoxetine, a serotonin specific reuptake inhibitor. The results indicate that the mode of action of polysaccharides from Banxia-houpu decoction in depression might be related to both 5-HT and DA systems.     

半夏厚朴汤抗抑郁活性部位的筛选

目的:筛选半夏厚朴汤的抗抑郁活性部位。方法:选用小鼠行为绝望模型评价抗抑郁作用;用荧光分光光度法测定单胺类神经递质。结果:半夏厚朴汤提取物(AE)和其4个部位均不同程度地降低绝望模型中小鼠游泳和悬尾的不动时间,具有一定的时效关系。其中以半夏厚朴汤提取物(AE)、石油醚提取物(AE-1)和水溶性部分(AE-4)最为显著,相互间无显著性差异。半夏厚朴汤提取物(AE)可显著地提高纹状体中5-HT含量和皮层中NE含量,而对其他脑区中神经递质无显著性影响。石油醚提取物(AE-1)可显著地提高纹状体中5-HT含量和皮层中NE和DA含量,氯仿提取物(AE-2)能极显著地提高皮层中DA含量。结论:半夏厚朴汤具有抗抑郁作用,其活性成分主要分布在石油醚和水溶性部位。半夏厚朴汤可能是部分地通过对单胺类神经递质系统的整合而达到抗抑郁目的。     

桂枝解郁方不同工艺抗抑郁作用的比较

目的:比较桂枝解郁方不同工艺的抗抑郁作用。方法:本实验将小鼠随机分成4组,即桂枝解郁方-A组、桂枝解郁方-B组(分别ig给予桂枝解郁液-A和桂枝解郁液-B 12.66 g.kg-1,每天1次,连续给药10 d)、盐酸阿米替林组(实验前3 dig给予盐酸阿米替林50 mg.kg-1,每天1次)、空白对照组(给予等体积的生理盐水)。采用小鼠强迫游泳实验、悬尾实验、自主活动实验和利血平拮抗实验,以小鼠不动时间、自主活动数和体温下降值为指标来评价桂枝解郁方不同工艺抗抑郁的作用。结果:在强迫游泳实验和悬尾实验中,桂枝解郁方-A能明显缩短小鼠的不动时间(P<0.05);在自主活动实验中,各组小鼠之间无显著性差异。利血平拮抗实验中,桂枝解郁方-A在4h能显著拮抗利血平诱发的小鼠体温降低(P<0.05)。结论:桂枝解郁方-A的抗抑郁作用优于桂枝解郁方B。     

复方柴胡口服液抗抑郁作用初步研究

目的:初步探讨复方柴胡口服液抗抑郁作用.方法:采用小鼠悬尾实验及强迫游泳实验等方法观察复方柴胡口服液的抗抑郁作用.结果:在小鼠强迫游泳实验和小鼠悬尾实验中,复方柴胡口服液低剂量(生药4g/kg)能明显缩短两种"行为绝望"模型小鼠的不动时间,中剂量(生药12g/kg)能明显缩短小鼠强迫游泳的不动时间.结论:复方柴胡口服液对"行为绝望"动物模型有抗抑郁作用.     

逍遥散和丹栀逍遥散抗抑郁作用的实验研究

目的 :探讨逍遥散、丹栀逍遥散抗抑郁作用。方法 :采用自主活动、小鼠悬尾实验及强迫游泳等方法观察逍遥散和丹栀逍遥散抗抑郁作用。结果 :逍遥散和丹栀逍遥散均能明显缩短小鼠悬尾和强迫游泳不动时间 (P <0 .0 5或P <0 .0 1) ,且对自主活动无影响。结论 :逍遥散和丹栀逍遥散均有明显的抗抑郁作用。     

达维胶囊对精神分裂症阴性症状小鼠的治疗作用及机理研究

目的：研究达维胶囊（达维）对精神分裂症阴性症状模型小鼠的治疗作用及相关机理。方法：注射低于麻醉剂量的氯胺酮（30mg／kg），制作精神分裂症阴性症状动物模型，用强迫游泳法测定各组小鼠在游泳时保持不动时间，评价达维胶囊对精神分裂症阴性症状小鼠的治疗效果。并用荧光分光光度法测定小鼠全脑内及血清中神经递质（DA，NA，5-HT）含量，探讨其作用机制。结果：与模型组相比，达维大、中剂量组及氯氮平组能使小鼠强迫游泳保持不动时间明显缩短，脑内及血中5-HT含量明显降低，血中NE水平明显升高。结论：达维胶囊对精神分裂症的阴性症状小鼠有一定的治疗作用，其作用机理可能与其能调节脑内5-HT和NE能神经系统功能有关。     

Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant‐Like Effects in Olfactory Bulbectomized Mice

Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain‐derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin‐related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5‐bromo‐2′‐deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX‐induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein after 3 h. The present data indicate that magnolol exerts antidepressant‐like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin‐related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd.     

基于均匀设计法评价柴胡-黄芩的配伍比例及抗抑郁机制

目的:研究柴胡-黄芩药对发挥抗抑郁功效的最佳配伍比例,探讨其可能的抗抑郁机制。方法:取柴胡、黄芩在2015年版《中国药典》中的规定用量,按照二因素七水平均匀设计表进行配伍分组。采用慢性不可预见温和应激(CUMS)方法造模,抑郁症模型小鼠灌胃给予柴胡-黄芩不同配伍比例的水煎剂,观察其对模型小鼠糖水偏好、强迫游泳、悬尾、开野等行为学试验的影响。将所得数据进行回归分析,通过回归方程求解最佳配伍比例。对优选的配伍比例进行验证,并测定小鼠脑海马环磷腺苷反应元件结合蛋白(CREB)磷酸化的水平及脑源性神经营养因子(BDNF)的表达,探讨柴胡-黄芩药对可能的抗抑郁机制。结果:与空白组小鼠相比,模型组小鼠糖水偏好率显著降低(P 0. 01),开野穿格次数显著减少(P 0. 01),强迫游泳不动时间和悬尾不动时间显著延长(P 0. 01);给予柴胡-黄芩水煎剂可增加模型小鼠的糖水偏好率(P 0. 05,P 0. 01)和穿格次数(P 0. 05,P 0. 01),缩短强迫游泳不动时间和悬尾不动时间(P 0. 05,P 0. 01)。验证试验显示,柴胡与黄芩配伍后可改善模型小鼠抑郁样行为,增加小鼠的糖水偏好率(P 0. 01),缩短强迫游泳不动时间和悬尾不动时间(P 0. 05,P 0. 01);柴胡-黄芩(1∶1)配伍组及柴胡-黄芩(8∶3)配伍组均可显著增加模型小鼠穿格次数(P 0. 05,P 0. 01);柴胡-黄芩(1∶1)配伍组在强迫游泳试验和悬尾试验中优于柴胡-黄芩(3∶8)和(8∶3)配伍组(P 0. 05,P 0. 01),在糖水偏好试验和开野试验中显著优于柴胡-黄芩(3∶8)配伍组(P 0. 05),且柴胡-黄芩(1∶1)配伍组促进海马中CREB磷酸化和增加海马中BDNF表达的效果最佳。结论:柴胡-黄芩药对可改善CUMS小鼠抑郁样行为,发挥抗抑郁功效,其最佳配伍比例为1∶1,最佳用量均约为5 g,其抗抑郁的作用机制可能与促进海马中CREB磷酸化和增加海马中BDNF表达有关。     

天麻乙酸乙酯提取物对行为绝望小鼠的抗抑郁作用

目的:研究天麻乙酸乙酯提取物(EtoAc extracts of Gastrodia elata,EEG)的抗抑郁作用.方法:雄性小鼠随机分为空白对照组,氟西汀组(20 mg·kg-1),氯丙咪嗪组(20 mg·kg-1),EEG低、高剂量组(0.063,0.126 g·kg-1),每组连续ig给药7d后,观察小鼠在悬尾实验(tail suspension test,TST),强迫游泳实验(forced swimming test,FST)中不动时间的变化情况以及小鼠在开场实验中自主活动的变化情况.结果:EEG高剂量(0.126 g·kg-1)能明显缩短小鼠悬尾不动时间,EEG高、低剂量(0.126,0.063 g·kg-1)均能明显缩短小鼠强迫游泳不动时间.EEG高、低剂量对小鼠在开场实验中的自主活动次数没有明显影响.结论:天麻乙酸乙酯提取物对“行为绝望”小鼠有抗抑郁作用.     

Antidepressant‐like effects of 20(S)‐protopanaxadiol in a mouse model of chronic social defeat stress and the related mechanisms

20(S)‐Protopanaxadiol (PPD) is a basic aglycone of the dammarane triterpenoid saponins and exerts antidepressant‐like effects on behaviour in the forced swimming test (FST) and tail suspension test (TST) and in rat olfactory bulbectomy depression models. However, the antidepressant effects of PPD have not been studied thoroughly. The objective of the present study was first to investigate the effect of PPD on depression behaviours induced by chronic social defeat stress (CSDS) in mice. The results showed that CSDS was effective in producing depression‐like behaviours in mice, as indicated by decreased responses in the social interaction test, sucrose preference test, TST, and FST, and that this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) and monoamines (5‐HT and NE) in the hippocampus and serum corticosterone levels. Additionally, western blot analysis revealed that CSDS exposure significantly downregulated BDNF, p‐TrkB/TrkB, p‐Akt/Akt, and p‐mTOR/mTOR protein expression in the hippocampus. Remarkably, chronic PPD treatment significantly ameliorated these behavioral and biochemical alterations associated withCSDS‐induced depression. Our results suggest that PPD exerts antidepressant‐like effects in mice with CSDS‐induced depression and that this effect may be mediated by the normalization of neurotransmitter and corticosterone levels and the alleviation of oxidative stress, as well as the enhancement of the PI3K/Akt/mTOR‐mediated BDNF/TrkB pathway.     

高度富集黄酮类成分的贯叶连翘提取物抗抑郁作用

目的探讨贯叶连翘提取物中高度富集的黄酮类成分的抗抑郁作用。方法采用小鼠强迫游泳实验、小鼠悬尾实验、开野实验和拮抗利血平所致的体温降低实验,分别以小鼠不动时间、自主活动数和体温下降值作为评价指标。结果在强迫游泳和悬尾实验中,40,80,160,240mg/kg剂量组贯叶连翘提取物均能显著缩短小鼠不动时间,20mg/kg剂量组无显著性差异;开野实验结果表明给药后小鼠的自主活动不同程度地减少;在利血平拮抗实验中,30,60,120mg/kg剂量组在3h,4h和5h各时间点体温下降值与模型对照组相比有显著性差异,240和480mg/kg两剂量组在各测定时间点体温下降值与模型对照组相比均有显著性差异。结论高度富集总黄酮的贯叶连翘提取物(弃除贯叶金丝桃素)有抗抑郁作用。     

抗郁汤对PSD小鼠自发性行为和外周血清5-羟色胺(5-HT)影响

[目的]观察抗郁汤对PSD小鼠自发性行为和血清5-羟色胺(5-HT)影响。[方法]将60只小鼠按体重随机分组。采用阻断单侧颈总动脉制备脑缺血再灌注模型。使用不同剂量抗郁汤进行干预,通过悬尾、强迫游泳实验,实验第6天测定模型鼠自发性行为、血清5-羟色胺(5-HT)指标。[结果]小鼠悬尾累计静止时间,模型组比空白对照组长(P<0.05),高剂量组明显低于模型组(P<0.01),中剂量组高于阳性对照组(P<0.05);强迫游泳累计静止时间模型组比空白对照组长(P<0.05),高剂量组、中剂量组及阳性对照组均低于模型组(P<0.05);血清5-HT含量模型组低于对照组(P<0.01),高剂量组、中剂量组及阳性对照组均高于模型组(P<0.05)。[结论]抗郁汤干预可使PSD小鼠血清中5-HT水平明显增高,增强自发性行为。