罗布麻叶抗抑郁活性部位的筛选

目的:筛选罗布麻叶的抗抑郁活性部位,并探讨抗抑郁活性与总黄酮含量的关系。方法:用小鼠强迫游泳实验评价抗抑郁作用;用荧光分光光度法测定单胺类神经递质;用紫外分光光度法测定总黄酮的含量。结果:罗布麻叶乙醇提物对小鼠的不动时间没有显著的影响,而其他4个部位均可不同程度的降低小鼠的不动时间,其中正丁醇部位和水相部位的作用最强。罗布麻叶乙醇提取物显著降低了5-HT在纹状体中的浓度,而石油醚、乙酸乙酯、正丁醇和水相部位对NA、DA、5-HT在海马,纹状体中的浓度有不同程度的影响。结论:罗布麻叶醇提物没有抗抑郁活性,但其他四个部位具有抗抑郁活性,其活性成分主要分布在正丁醇和水溶性部位,且抗抑郁活性与总黄酮含量没有线性关系。     

解郁方对抑郁模型小鼠脑内单胺类神经递质及单胺氧化酶含量的影响

目的研究解郁方抗抑郁作用的机理。方法采用酶联免疫检测试剂盒测定小鼠脑组织中单胺类神经递质含量;分光光度计法检测小鼠脑组织中单胺氧化酶(monoamine oxidase,MAO)活性,来研究解郁方抗抑郁作用的机制。结果解郁方Ⅰ和Ⅱ(12.00、6.00 g·kg-1)组均可显著升高小鼠脑内去甲肾上腺素、5-羟色胺、多巴胺(分别为P<0.01,P<0.05),解郁方Ⅰ和Ⅱ组可显著降低MAO活性(分别为P<0.01,P<0.05)。结论解郁方可能是通过抑制MAO活性,使突触间隙的单胺类神经递质含量升高,而起到抗抑郁作用。     

AQP4参与雌激素对单胺类神经递质的调节作用

目的：探讨AQP4对雌激素调节神经递质作用的影响。方法：应用雄性AQP4基因敲除型CD1小鼠与野生型CD1小鼠，给予不同剂量雌激素后测定不同脑区中单胺类神经递质的含量。结果：AQP4基因敲除型雄性小鼠纹状体多巴胺（DA）及5-羟色胺（5-HT）、皮层去甲肾上腺素（NE）含量增加；海马NE、下丘脑DA水平下降。同时，给予雌激素后，野生型雄性CD1小鼠纹状体DA、5-HT含量及海马5-HT含量升高，皮层DA、5-HT水平及下丘脑NE、DA水平下降；而雌激素对AQP4敲除型雄性CD1小鼠单胺类递质无显著影响。结论：AQP4敲除可改变雌激素对单胺类递质水平的调节作用，对纹状体内DA水平的影响尤为显著。AQP4参与了雌激素对单胺类神经递质的调节。     

蒲公英总黄酮提取液对衰老模型小鼠脑组织单胺氧化酶及单胺类神经递质含量的影响

目的:探讨蒲公英总黄酮提取液对衰老模型小鼠脑组织单胺氧化酶(MAO)及单胺类神经递质含量的影响.方法:采用小鼠注射D-gal制成衰老模型,蒲公英总黄酮提取液灌胃30d,测定小鼠脑组织MAO活性及单胺类神经递质的含量.结果:蒲公英总黄酮提取液能降低衰老模型小鼠脑组织内MAO活性(P＜0.05),提高去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)含量(P＜0.05).结论:蒲公英总黄酮提取液可降低衰老模型小鼠脑组织MAO活性并能提高单胺类神经递质的含量,具有一定的抗衰老作用.     

天麻醇提取物对小鼠的抗抑郁作用

目的:对天麻乙醇提取物(ethanolic extracts ofGastrodia elata,EEGE)的抗抑郁作用机制进行研究。方法:用药物给小鼠灌胃7d后,观察小鼠在悬尾试验,强迫游泳试验中不动时间的变化情况以及小鼠开野试验中自主活动变化情况。用荧光分光光度法测定小鼠脑组织中海马区和纹状体区单胺递质去甲肾上腺素(NA)、多巴胺(DA)、五羟色胺(5-HT)含量。结果:200,300mg.kg-1EEGE可以明显缩短小鼠在强迫游泳试验、悬尾试验中不动时间,100mg.kg-1的醇提物有降低不动时间的趋势,但效果不明显;300mg.kg-1提取物的效果比阳性对照抗抑郁药氟西汀的作用还强。无论实验剂量的EEGE还是氟西汀对小鼠的自主行为均没有显著的影响。与空白组相比,200、300mg.kg-1EEGE显著提高了海马区NA的浓度;各剂量EEGE均显著降低纹状体中DA的浓度;各剂量EEGE均显著提高纹状体中5-HT的浓度。结论:天麻醇提物对抑郁模型小鼠具有显著的抗抑郁作用。可能与它能改变小鼠脑内海马、纹状体的单胺类神经递质浓度水平有关。     

逍遥散不同提取部位对慢性轻度不可预知应激模型大鼠行为学及海马中单胺类神经递质的影响

建立了慢性轻度不可预知应激(CUMS)模型大鼠,分别灌胃给予逍遥散石油醚部位(1)、95%乙醇部位(2)、1+2及盐酸文拉法辛(阳性药),考察大鼠行为学和海马中单胺类神经递质(去甲肾上腺素、5-羟色胺和5-羟基吲哚乙酸)的变化。采用旷场试验和糖水消耗试验结果及大鼠体重评价其行为学改变,并以HPLC-电化学方法检测海马内单胺类神经递质的含量。结果表明,单用1及1+2联用与阳性药具有相似的抗抑郁效果,对大鼠行为学和3种神经递质的回调均有显著改善;而单用2的疗效不显著,在3种神经递质中仅对去甲肾上腺素有显著的回调作用。     

百合地黄汤不同萃取部位的镇静催眠活性研究

目的以果蝇为模式生物筛选百合地黄汤提取物镇静催眠的有效部位,并基于单胺类神经递质的水平对各有效部位的镇静催眠作用进行研究。方法百合地黄汤提取物依次用石油醚、二氯甲烷、乙酸乙酯和水饱和正丁醇萃取,分离得不同萃取部位,以果蝇失眠模型筛选镇静催眠有效部位,并研究各有效部位对果蝇脑部单胺类神经递质的影响。结果与空白组相比,模型组果蝇总睡眠时间显著缩短(P<0.01);与模型组相比,百合地黄汤全方低、中、高剂量组果蝇总睡眠时间明显延长(P<0.05),石油醚部位低剂量组、二氯甲烷部位中剂量组、乙酸乙酯部位中剂量组以及水饱和正丁醇部位低剂量组果蝇总睡眠时间明显延长(P<0.05);各有效部位组果蝇脑部多巴胺(DA)及其代谢物高香草酸(HVA)含量降低,5-羟色胺(5-HT)及其代谢物5-羟吲哚乙酸(5-HIAA)含量升高。结论百合地黄汤提取物的石油醚、二氯甲烷、乙酸乙酯以及水饱和正丁醇部位均有镇静催眠作用,推测各有效部位的镇静催眠作用可能与调节脑部单胺类神经递质水平相关。     

解郁汤对慢性应激抑郁模型小鼠的抗抑郁作用及机制研究

目的：探讨解郁汤的抗抑郁作用及可能机制。方法：以慢性轻度不可预见性应激方法建立小鼠抑郁症模型,以糖水消耗、悬尾实验、强迫游泳实验、开野实验进行行为学评分,并通过UPLC—T—QMS系统检测其脑内单胺类神经递质的含量,观察模型小鼠给药前后的变化。通过免疫组化检测小鼠海马区BDNF以及5-Brdu表达。结果：与空白组相比．模型组的小鼠蔗糖水消耗量明显下降,强迫游泳不动时间、悬尾不动时间均显著增加,交叉次数、直立次数显著减少,脑内的去甲肾上腺素、5-羟色胺、5-羟色胺吲哚乙酸含量降低（P〈0．05）。与模型组相比,解郁汤组小鼠蔗糖水消耗量显著升高,强迫游泳不动时间、悬尾不动时间均显著减少（P〈0．05）。解郁汤能显著增加大鼠脑内去甲肾上腺素、5-羟色胺、5-羟色胺吲哚乙酸含量（P〈0．05）。解郁汤能增加小鼠脑内海马区BDNF以及5-Brdu表达。结论：解郁汤具有抗抑郁作用,其作用机制可能与调节中枢单胺类神经递质的调节以及促进海马神经元再生有关。     

遍地金不同提取物的抗抑郁作用

目的筛选遍地金提取物的抗抑郁活性组分,并初步了解各活性组分的抗抑郁作用机制。方法将遍地金提取物分为3个不同的组分,应用6种抗抑郁药理模型筛选抗抑郁活性组分。结果提取物中所有组分的中、小剂量均可显著增加大鼠成功逃避次数,大剂量均可显著减少小鼠的游泳不动时间;水、正丁醇提取组分各个剂量均可显著减少小鼠的悬尾不动时间。但5-HTP致小鼠甩头行为实验中,各组分无显著性差异;利血平及阿朴吗啡引起的体温降低试验中,各组分也无显著性差异。结论遍地金的水、正丁醇提取组分均有较好的抗抑郁作用,水提取组分的效果最佳,正丁醇提取组分次之。     

静安口服液对中枢神经系统单胺类介质的影响研究

目的观察静安口服液对小鼠脑内单胺类神经递质及其代谢产物的影响。方法采用高效液相-电化学检测器对小鼠脑内单胺类神经递质及其代谢产物进行测定。结果3个剂量组均能显著降低小鼠脑内多巴胺的含量,同时可显著提高小鼠脑内5-羟色胺的代谢产物5-羟吲哚乙酸含量。结论静安口服液具有调节上述递质含量的作用,可能是该方治疗小儿多发性抽动症的有效机制之一。     

The antidepressant effect of ethanol extract of radix puerariae in mice exposed to cerebral ischemia reperfusion

In our pilot study, the depressive-like behaviors of mice exposed to cerebral ischemia reperfusion (CIR) were observed and the antidepressant effects of radix puerariae (RP; root of the Pueraria plant) extract in CIR mice were assessed because it was speculated that the neuronal damage caused by CIR played an important role in the development of poststroke depression (a common and severe complication after stroke) and the RP extract was reported to exhibit effect of neuronal protection from cerebral ischemia damage. Our studies above indicated that the RP extract markedly shortened the increased immobility time induced by CIR of male mice in the forced swimming test (FST) and tail suspension test (TST), indicating a possible antidepressant activity. Thus, the aim of the present study was to confirm the putative antidepressant effect of RP extract (75, 150, and 300 mg/kg, administered orally 24 h after the CIR) on reserpine-induced symptoms. To get further insight into the mode of antidepressant action of RP extract, biochemical examination was conducted concomitantly to examine possible involvement of the brain monoamine systems in the behavioral syndromes observed. In CIR mice, pronounced low levels of norepinephrine (NE) and 4-dihydroxyphenylacetic acid (DOPAC, a metabolite of dopamine) in the hippocampus or striatum were detected, which were reversed by RP extract, whereas no significant change of serotonin (5-HT) was detected in either CIR or RP extract-treated mice. The data suggested that the disturbance of NE and DA systems in hippocampus and striatum played more important roles in the development of depressive-like behavior of CIR mice than 5-HT system did, and RP extract ameliorated the abnormal symptoms caused by CIR, which may throw new lights on the treatment of poststroke depression.     

黄芩总黄酮对大鼠脑核团单胺类递质的影响

目的研究黄芩总黄酮对大鼠脑内不同神经核团中单胺类神经递质的影响。方法用高效液相色谱-电化学检测法,测定大鼠静脉给予单剂量黄芩总黄酮后单胺类神经递质及代谢产物在脑内不同神经核团的含量变化。结果给予大鼠黄芩总黄酮后,海马和皮层中多巴胺的含量升高,而纹状体内多巴胺的含量降低。结论黄芩总黄酮影响大鼠脑内不同神经核团多巴胺的含量,在海马纹状体影响明显。     

Effects of acute and chronic administration of antidepressant drugs on the central cholinergic nervous system: Comparison with anticholinergic drugs

The purpose of this investigation was to study the effects of antidepressant drugs on the central cholinergic system of the rat after acute and chronic administration. Drugs (antidepressants and non-antidepressants) were first divided into highly potent, moderately potent or weak anticholinergic categories based upon the ability of each compound to displace [³H]-QNB ([³H]quinuclidinyl benzilate from synaptosomal membranes. One antidepressant drug and one non-antidepressant drug, with similar anticholinergic properties, were chosen as representative agents of each category of anticholinergic potency. Acute administration of amitriptyline or atropine (highly potent anticholinergics) increased the level of high affinity uptake of choline in the hippocampus and striatum. Imipramine and thioridazine (moderately potent anticholinergics) increased the uptake of choline only in the striatum. After acute administration, the effects of nomifensine and d-amphetamine (weak anticholinergics) differed on striatal uptake of choline. Following 30 days pretreatment with any drug, an acute challenge dose of that drug no longer altered the uptake of choline in either region. After chronic administration, amitriptyline increased the density of muscarinic receptors in the cortex whereas atropine increased the density of receptors in the cortex, hippocampus and striatum. The other agents did not alter receptor parameters in the regions examined. Since the central cholinergic actions of the antidepressants were similar to the central actions of the non-antidepressants, it is concluded that the effects of the antidepressants on the central cholinergic nervous system are more closely related to the side effects of these agents than to their therapeutic mechanism of action.     

胡椒碱及其衍生物3,4-次甲二氧桂皮酰哌啶的抗抑郁作用

目的研究胡椒碱及其衍生物3,4次甲二氧桂皮酰哌啶的抗抑郁作用,并对其作用机理进行初步探讨。方法利用小鼠强制游泳实验、悬尾实验等考察胡椒碱和3,4次甲二氧桂皮酰哌啶的抗抑郁作用,并通过测定不同脑区内单胺类神经递质质量浓度以及全脑单胺氧化酶活性变化,探讨作用机制。结果胡椒碱和3,4次甲二氧桂皮酰哌啶(10、20 mg.kg-1)长期给药后,能明显缩短小鼠在行为学实验中的不动状态时间,并且该作用随剂量增大效应逐渐降低,高剂量(80 mg.kg-1)表现出明显的中枢神经抑制作用;能显著提高脑内5羟色胺水平,而对脑内肾上腺素递质水平未见明显影响;具有较弱的单胺氧化酶抑制作用。结论胡椒碱和3,4次甲二氧桂皮酰哌啶具有较好的抗抑郁作用,其作用是通过上调中枢神经系统5羟色胺或多巴胺水平实现的。     

Antidepressant-like effects of piperine and its derivative,antiepilepsirine

In the present study, antidepressant-like effects of piperine (PIP) and its derivative, antiepilepsirine (AES), were investigated in two depressive models: forced swimming test (FST) and tail suspension test (TST). To further explore the mechanisms underlying their antidepressant-like activities, the brain monoamine levels and monoamine oxidase A and B (MAO-A and MAO-B) activities were also determined. The research results for the first time indicated that after two weeks of chronic administration, PIP and AES at doses of 10–20 mg/kg significantly reduced the duration of immobility in both FST and TST, without accompanying changes in locomotor activity in the open-field test. But at the dose of 80 mg/kg, the antidepressant activity of both PIP and AES returned to the control level in the TST and FST. In the monoamine assay, chronic AES administration significantly elevated the dopamine level in striatum, hypothalamus and hippocampus, and also increased the serotonin level in the hypothalamus and hippocampus. In contrast, chronic treatment of PIP only enhanced the serotonin level in the hypothalamus and hippocampus but did not influence the dopamine level. Moreover, both PIP and AES showed no effects on level of noradrenaline in these brain regions. The MAO activity assay also indicated that PIP and AES showed a minor MAO inhibitory activity. In the present study, we demonstrated that the antidepressant-like effects of PIP and AES might depend on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake. Antidepressant properties of PIP were supposed to be mediated via the regulation of serotonergic system, whereas the mechanisms of antidepressant action of AES might be due to its dual regulation of both serotonergic and dopaminergic systems.     

Antidepressant-like effects of piperine and its derivative, antiepilepsirine

In the present study, antidepressant-like effects of piperine (PIP) and its derivative, antiepilepsirine (AES), were investigated in two depressive models: forced swimming test (FST) and tail suspension test (TST). To further explore the mechanisms underlying their antidepressant-like activities, the brain monoamine levels and monoamine oxidase A and B (MAO-A and MAO-B) activities were also determined. The research results for the first time indicated that after two weeks of chronic administration, PIP and AES at doses of 10-20 mg/kg significantly reduced the duration of immobility in both FST and TST, without accompanying changes in locomotor activity in the open-field test. But at the dose of 80 mg/kg, the antidepressant activity of both PIP and AES returned to the control level in the TST and FST. In the monoamine assay, chronic AES administration significantly elevated the dopamine level in striatum, hypothalamus and hippocampus, and also increased the serotonin level in the hypothalamus and hippocampus. In contrast, chronic treatment of PIP only enhanced the serotonin level in the hypothalamus and hippocampus but did not influence the dopamine level. Moreover, both PIP and AES showed no effects on level of noradrenaline in these brain regions. The MAO activity assay also indicated that PIP and AES showed a minor MAO inhibitory activity. In the present study, we demonstrated that the antidepressant-like effects of PIP and AES might depend on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake. Antidepressant properties of PIP were supposed to be mediated via the regulation of serotonergic system, whereas the mechanisms of antidepressant action of AES might be due to its dual regulation of both serotonergic and dopaminergic systems.     

Antidepressant-like effects of piperine and its derivative, antiepilepsirine

In the present study, antidepressant-like effects of piperine (PIP) and its derivative, antiepilepsirine (AES), were investigated in two depressive models: forced swimming test (FST) and tail suspension test (TST). To further explore the mechanisms underlying their antidepressant-like activities, the brain monoamine levels and monoamine oxidase A and B (MAO-A and MAO-B) activities were also determined. The research results for the first time indicated that after two weeks of chronic administration, PIP and AES at doses of 10-20 mg/kg significantly reduced the duration of immobility in both FST and TST, without accompanying changes in locomotor activity in the open-field test. But at the dose of 80 mg/kg, the antidepressant activity of both PIP and AES returned to the control level in the TST and FST. In the monoamine assay, chronic AES administration significantly elevated the dopamine level in striatum, hypothalamus and hippocampus, and also increased the serotonin level in the hypothalamus and hippocampus. In contrast, chronic treatment of PIP only enhanced the serotonin level in the hypothalamus and hippocampus but did not influence the dopamine level. Moreover, both PIP and AES showed no effects on level of noradrenaline in these brain regions. The MAO activity assay also indicated that PIP and AES showed a minor MAO inhibitory activity. In the present study, we demonstrated that the antidepressant-like effects of PIP and AES might depend on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake. Antidepressant properties of PIP were supposed to be mediated via the regulation of serotonergic system, whereas the mechanisms of antidepressant action of AES might be due to its dual regulation of both serotonergic and dopaminergic systems.     

两种LC乙醇提取物急性毒性试验毒性比较

目的通过两种LC乙醇提取物的急性毒性试验,比较二者的毒性。方法24h内小鼠单次灌胃给予两种LC乙醇提取物,观察毒性反应及死亡情况,测定最大耐受量、最小致死量。结果LC乙醇提取物Ⅰ的最大耐受量为5．243g／kg．bw,最小致死量为6．554g／kg．bw;LC乙醇提取物Ⅱ的最大耐受量为5．760g／kg．bw,最小致死量为7．200g／kg．bw。结论LC乙醇提取物Ⅰ的毒性略比LC乙醇提取物Ⅱ大。