钩吻素子对大鼠焦虑行为的影响

目的进一步明确钩吻素子是否具有抗焦虑作用。方法以大鼠高架十字迷宫实验为动物模型,评价钩吻素子单次皮下注射给药和连续皮下注射给药的抗焦虑活性及特点。结果钩吻素子能显著增加大鼠进入高架十字迷宫开臂次数和在开臂的停留时间百分率(P<0.05,P<0.01);钩吻素子在实验剂量下对大鼠自主运动活性无影响(P>0.05)。结论钩吻素子可能具有抗焦虑作用。     

吲哚衍生物I_(20)的抗焦虑作用及机制研究

目的　研究外周型苯二氮卓受体配基吲哚衍生物I2 0的抗焦虑作用及作用机制。方法　在小鼠高架十字迷宫模型和小鼠明暗箱模型上评价I2 0 的抗焦虑活性 ,用放免法测定给予不同剂量的I2 0 在不同时间点大鼠血清中神经类固醇孕酮的含量。结果　I2 0 (1mg·kg-1,ip)能增加小鼠在开臂内运动时间百分率和小鼠穿箱次数 ,在小鼠高架十字迷宫与明暗箱模型上显示出抗焦虑作用 ;I2 0 在实验剂量下 (2 0mg·kg-1,ip)对小鼠自主活动性无影响 ,表明该化合物在抗焦虑的剂量下无镇静的副作用。放免测定结果表明 ,I2 0 能剂量依赖与时间依赖地增加大鼠血清中孕酮的含量。结论　I2 0 可能是通过与外周型苯二氮卓受体结合 ,增加体内神经类固醇孕酮的释放 ,间接调控GABAA 受体的功能来发挥抗焦虑作用     

缬草素抗焦虑作用及其机制的初探

目的研究缬草素的抗焦虑作用,并分析其可能的作用机制。方法以大鼠高架十字迷宫实验和开场实验为动物模型,考察缬草素的抗焦虑活性;用酶联免疫吸附法(ELISA)测定大鼠血清皮质酮的水平。结果缬草素(10mg.kg-1)能增加大鼠在开臂内运动时间和次数百分率,并且提高大鼠在开场中央区的次数,在大鼠高架十字迷宫与开场模型上显示出抗焦虑作用;酶联免疫吸附法表明:缬草素能降低大鼠血清皮质酮水平。结论缬草素具有明显的抗焦虑作用,机制可能与调节下丘脑-垂体-肾上腺轴功能有关。     

天麻及其酚类化合物对小鼠的抗焦虑作用

天麻Gastrodia elata Blume的抗焦虑作用研究鲜有报道。因此,作者进行了以下试验,研究该植物根茎水提取物(AEGE)以及所含的酚类化合物4-羟基苄醇(HA)和4-羟基苯甲醛(HD)对小鼠在高架十字迷宫实验中的抗焦虑作用,并观察了AEGE与氟马西尼或WAY 100635同服对AEGE抗焦虑作用的影响。选用雄性ICR小鼠。在开场实验中,小鼠给以AEGE50、100、200、400 mg/kg,HA或HD5、10、25、50、100 mg/kg,记录给药1h后小鼠5min内水平运动能力。在高架十字迷宫(EPM)实验中,记录给以试药(剂量同上)1h后,小鼠5min内进入开臂或闭臂的次数与停留时间,以…     

核黄素四丁酸酯抗焦虑作用的药效学分析

目的了解核黄素四丁酸酯的抗焦虑作用。方法以空白和地西泮为对照,采用小鼠高架十字迷宫实验,评价RTB抗焦虑作用。结果与空白组比较,各给药组的总入臂次数(OE+CE)均有提高,但未有统计学差异(P>0.05),提示各组药物均未改变动物的活动能力。地西泮和RTB均能提高小鼠的OE%值,但未见RTB对小鼠的OE%有统计学差异(P>0.05),而地西泮能显著提高小鼠的OE%。与空白组比,RTB小剂量组能显著提高小鼠的OT%,并有统计学差异(P<0.05)。结论 RTB具有抗焦虑作用,且不影响小鼠的运动活力。     

组胺与扑尔敏对焦虑的影响

目的观察和分析组胺与扑尔敏对焦虑的影响。方法选用小鼠高架十字迷宫实验和小鼠明暗箱实验分别测定各组小鼠进入开放臂和封闭臂的总次数(OE+CE)、进入开放臂次数百分比(OE%)、开放臂停留时间比例(OT%)、探究次数(HT)和封闭臂后腿直立次数(RT)、明暗箱中的穿箱次数(TT)和在明箱停留时间的百分比(LT%)。结果剂量为4.44×l0-6g·kg-1的组胺(HA)能显著减少小鼠的OT%(P>0.05);4.00×l0-3g·kg-1的扑尔敏以及同剂量的扑尔敏加4.44×l0-6g·kg-1HA能显著增加小鼠的OE+CE、OE%、OT%、TT、LT%(P>0.01)。结论扑尔敏具有抗焦虑的作用,外周给予一定量的HA可以通过H1受体发挥促进焦虑的作用。     

四氢孕酮和地西泮对暴露于架高十字迷宫小鼠的作用

目的比较孕酮的还原性代谢产物四氢孕酮和地西泮抗焦虑作用。方法C57小鼠腹腔注射四氢孕酮、地西泮或赋形剂 ,20min后观察在架高十字迷宫试验中的表现 ,测定其自发活动。结果腹腔注射四氢孕酮0.1mg·kg-1,明显缩短小鼠进入十字迷宫开臂的潜伏期[从(31.30±8.39)s减少到(8.80±6.00)s ,P<0.001] ,并显著增加进入十字迷宫开臂的次数(从1.20±0.42增到4.80±1.75,P<0.001)及在开臂的滞留时间占总时间的百分比 (从7.13 %增加到32.50 %,P<0.001)。而腹腔注射地西泮0.25mg·kg-1的抗焦虑作用弱于四氢孕酮。自发活动实验显示 ,0.5mg·kg-1地西泮明显减少小鼠自发活动 (P<0.01) ,而0.1mg·kg-1地西泮和0.25mg·kg-1 的四氢孕酮均不影响小鼠自发活动。结论试验结果提示神经甾体和地西泮对小鼠行为有不同的作用。四氢孕酮具选择性抗焦虑作用而不影响自发活动 ,可望成为地西泮抗焦虑的代用品     

谷维素和维生素B1增强地西泮的抗焦虑作用

目的研究地西泮、谷维素和维生素B1按1∶32∶8的比例合用后的抗焦虑作用,并同地西泮比较.方法采用大、小鼠高架十字谜宫模型和大鼠五甲烯四氮唑辨别效应对抗模型.结果在大、小鼠高架十字迷宫实验中,地西泮与谷维素和维生素B1合用后,大、小鼠在开放臂停留时间百分率明显增加,表现出明显的抗焦虑作用;而且其在开放臂停留时间百分率的增加,明显高于单独使用与其含量相等的地西泮的作用.在大鼠五甲烯四氮唑辨别效应对抗实验中,合用后对抗大鼠五甲烯四氮唑辨别效应的ED50值为23.4 mg·kg-1,其地西泮含量为0.6 mg·kg-1,远低于地西泮单方的ED50值3.5mg·kg-1.结论谷维素和维生素B1具有增强地西泮的抗焦虑作用.     

脑功肽组方对高架十字迷宫大鼠海马单胺类递质及其代谢物的影响

摘 要 目的：观察脑功肽组方对高架十字迷宫大鼠海马单胺类递质及其代谢产物含量的影响,探讨脑功肽组方抗焦虑作用的机制。方法: 采用大鼠高架十字迷宫焦虑动物模型（EPM）观察脑功肽组方2个剂量组对大鼠焦虑行为学的影响;采用高效液相色谱 荧光检测（HPLC FLD）法测定大鼠海马单胺类递质及其代谢产物的含量。结果:与空白对照组相比,脑功肽组方高剂量组进入开臂次数百分比、开臂停留时间百分比均显著提高（P＜0.05）,脑功肽低剂量组大鼠进入开臂次数百分比显著提高（P＜0.05）;脑功肽高剂量组大鼠海马5 羟色胺（5 HT）的含量与空白对照组相比显著降低（P＜0.05）,高香草酸（HVA）含量显著升高（P＜0.05）。结论:在EPM实验中,脑功肽组方显示其具有一定的抗焦虑作用,大鼠海马单胺类递质含量测定显示可能与降低大鼠海马5 HT含量有关。     

紫果西番莲叶提取物抗焦虑作用及其机制

目的探讨紫果西番莲叶提取物的抗焦虑作用及其机制。方法 60只小鼠随机分为空白对照组、阳性对照组和提取物大、中、小剂量组共5组。提取物大、中、小剂量组分别灌胃紫果西番莲提取物800,400,200 mg·kg-1·d-1,阳性对照组给予地西泮2 mg·kg-1·d-1,空白对照组灌胃等容积1%羧甲基纤维素钠,各组连续给药7 d。以高架十字迷宫(EPM)实验为动物模型,考察紫果西番莲叶的抗焦虑活性;用聚合酶链反应(PCR)法对扩增产物进行分析。结果紫果西番莲叶醇提物(400,800 mg·kg-1·d-1)能增加小鼠在开臂内运动时间和次数百分率,并且提高小鼠在开场中央区的次数;实时荧光定量PCR法分析表明,紫果西番莲叶醇提物(400,800 mg·kg-1·d-1)能上调EPM焦虑小鼠脑组织中GABAA受体α2亚型和α3亚型mRNA表达水平。结论紫果西番莲叶醇提物具有明显的抗焦虑作用,其作用机制可能与调节GABAA受体α2亚型和α3亚型mRNA表达水平有关。     

Anxiolytic and sedative effects of dehydroeffusol from Juncus effusus in mice

Dehydroeffusol, a phenanthrene isolated from Juncus effusus L., possesses characteristic anxiolytic and sedative properties, as determined by an array of behavioral tests in mice. In the elevated plus-maze test, dehydroeffusol significantly increased the number of entries into the open arms and the time the mice spent in these arms in a dose-dependent manner, with a minimum effective dose of 2.5 mg/kg. Dehydroeffusol also significantly increased the head-dips of mice in the hole-board test in a dose-dependent manner, with a minimum effective dose of 5 mg/kg. Dehydroeffusol reduced mouse locomotion in the open-field test with a minimum effective dose of 5 mg/kg. In the rota-rod test, 1-5 mg/kg dehydroeffusol did not decrease the fall-down time of mice. The above results confirm that dehydroeffusol possesses anxiolytic and sedative properties and does not affect the general movement coordination of mice. This suggests that dehydroeffusol is a novel anxiolytic chemical derived from herbal medicines.     

Anxiolytic-like effects of NMDA/glycine-B receptor ligands are abolished during the elevated plus-maze trial 2 in rats

Rationale Drugs enhancing the GABA_A and/or reducing the NMDA/glycine-B receptor activity produce an anxiolytic effect. Regarding the former drugs (e.g. benzodiazepines), prior elevated plus-maze (EPM) test experience abolishes the trial 2 anxiolytic activity, a phenomenon referred to as "one-trial tolerance" (OTT).Objectives The present study examined whether the OTT phenomenon occurs with drugs that reduce the NMDA/glycine-B receptor activity. Methods. Maze-naive and maze-experienced (prior EPM exposure) rats were treated with (±)-HA-966 (2.0 or 4.0 mg/kg), (+)-MK-801 (0.03 or 0.06 mg/kg) or memantine (4.0 or 8.0 mg/kg) and submitted to the EPM. To investigate whether the loss of drug responsiveness was due to pharmacological tolerance, rats received memantine (8.0 mg/kg) both 48 h and 30 min before the first EPM exposure.Results All drugs increased open arms exploration, indicating an anxiolytic effect, in maze-naive but not in maze-experienced rats, in which increased open arms avoidance was observed. An anxiolytic effect was also observed after repeated memantine administration in maze-naive/drug-experienced rats. These effects were observed in the absence of changes in enclosed arms entries, an EPM general exploratory activity index.Conclusions The present findings extend the OTT phenomenon to drugs that reduce the NMDA/glycine-B-receptor activity, and emphasize the repeated test exposure rather than repeated drug administration as a critical determinant for the drug anxiolytic activity. Considering the mechanisms by which the EPM experience alters the drug effects, the present findings favor the hypothesis in which the OTT phenomenon emerge as a consequence of the development and adoption of an anxiolytic-insensitive behavioral strategy.     

香椿叶总黄酮对糖尿病小鼠血糖的影响

目的研究香椿叶总黄酮对糖尿病小鼠血糖的影响。方法采用链脲佐菌素腹腔注射制备糖尿病小鼠模型,造模成功小鼠随机分为模型组、香椿叶总黄酮大剂量(800 mg·kg-1·d-1)、中剂量(400 mg·kg-1·d-1)和小剂量组(100 mg·kg-1·d-1),优降糖组(60mg·kg-1·d-1),连续给药30 d后,观察血糖的变化。结果香椿总黄酮可明显降低糖尿病小鼠的血糖。结论香椿叶总黄酮有明显的降糖作用,为临床上防治糖尿病提供了理论依据。     

Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats

This study investigated the effect of Withania somnifera Dunal (WS) root extract and diazepam in social isolation induced behavior such as anxiety and depression in rats. Rats were isolated for 6 weeks and the assessment of changed behavior were done on elevated plus maze (EPM) and forced swim test (FST). Isolation reared rats spent less time into the open arms on EPM and significantly increased immobility time in FST compared to group housed rats. WS (100, 200 or 500 mg/kg, oral) and diazepam (1 or 2 mg/kg, ip) dose dependently increased the time spent and entries into the open arms on EPM test and showed the anxiolytic activity. Subeffective dose of WS (50 mg/kg, oral) potentiated the anxiolytic action of diazepam (0.5, 1 or 2 mg/kg, ip). WS (100, 200 or 500 mg/kg, oral) also reduced the immobility time in FST, thus showed antidepressant effect in both group housed and social isolates. The investigations support the use of WS as a mood stabilizer in socially isolation behavior in Ayurveda.     

Regulative effect of aqueous extract of Eichhornia crassipes on the oxygen uptake capacity and motion responses of mice under wet/cool stress

OBJECTIVE To investigate the regulative effect of aqueous extract of Eichhornia crassipes on the oxygen uptake capacity and motion responses of mice under wet/cool stress. METHODS KM mice were randomly divided into normal control group,model control group,Eichhornia crassipes lowdose group(0.5g·kg-1)and high dose group(1.5g·kg-1),then performed intragastric administration for a period of 7d.Wet/cold stressed mice model was established using repeated intermittent(3h·d-1,consecutive 7d)exposure method by placing mice into the exposure box which was covered by ice at the bottom(T<0℃;RH>85%).Oxygen consumption was observed during exposure.Inclined plane method(muscle coordination capacity test)was performed immediately after exposure.60-second video of exhaustive swimming(to calculate swimming speed)was taken 1hafter the last exposure,the exhaustive swimming time was recorded.RESULTS(1)Compared with normal control group,model control group showed significant improvement in oxygen consumption(P<0.01),with an increase up to 77.33%,while inclined plate time,swimming speed and exhaustive swimming time showed significant reduction(P<0.01),at the rates 46.3%,8.54% and 19.68%respectively.(2)Compared with normal control group,Eichhornia crassipes low dose group and high dose group both improved oxygen consumption significantly(P<0.01),at rates of 10.93% and 90.38%respectively.This indicated high-dose aqueous extract of Eichhornia crassipes could fulfil actual oxygen demand of wet/cold stressed mice effectively.Inclined plate and exhaustive swimming experiments indicated that low-dose aqueous extract of Eichhornia crassipes boosted physical power significantly,as its exhaustive swimming time was increased up to 56.61%.Meanwhile,high-dose aqueous extract of Eichhornia crassipes has significant regulative effect on muscle coordination capability and motion speed,which were increased by 17.38% and 11.17%,respectively.CONCLUSION Aqueous extract of Eichhornia crassipes has definite regulative effect on the oxygen uptake capacity and motion responses of wet/cold stressed mice.Aqueous extract of Eichhornia crassipes can achieve stress protective effect by improving oxygen uptake capacity,muscle coordination capacity and motion abilities.     

Fascaplysin对ICR小鼠S180移植瘤的抑制作用及体内安全性的初步观察

目的：研究Fascaplysin对ICR小鼠移植性骨肉瘤S180瘤体的体内抑制作用。方法：急性毒性实验采用LD50数据处理程序1.01版计算LD50。皮下注射技术建立荷S180骨肉瘤的ICR小鼠动物模型,并随机分为空白对照组（注射生理盐水）、阳性对照组（CTX,30 mg.kg-1.d-1）、Fascaplysin高剂量组（20 mg.kg-1.d-1）和Fascaplysin低剂量组（5 mg.kg-1.d-1）共4组,观察相应处理10 d后各组小鼠移植瘤生长状况（抑瘤率）及瘤组织病理学形态变化。结果：阳性对照组、Fascaplysin高剂量组和Fascaplysin低剂量组的抑瘤率分别为（53±9）%、（52±10）%和（30±12）%;给药期间Fascaplysin对ICR小鼠肝、肾组织未产生明显的病理性影响,而对ICR小鼠体内S180移植瘤组织的病理性影响较为明显。结论：一定剂量的Fascaplysin对ICR小鼠S180移植性骨肉瘤生长具有较好的抑制作用,是一个有潜力的抗癌药物。     

Antagonism of AMPA receptors produces anxiolytic-like behavior in rodents: Effects of GYKI 52466 and its novel analogues

Rationale Although emerging number of data supports the role of glutamate receptors and the potential of their antagonists in anxiety disorders, the involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors in anxiety is less well characterized. Objective To evaluate the anxiolytic potential of 2,3-benzodiazepine (2,3BDZ) type AMPA receptor antagonists in various models of anxiety. Materials and methods Whole-cell currents, hippocampal field potentials, elevated plus maze (EPM), meta-chlorophenylpiperazine (mCPP)-induced anxiety model, Vogel test in rats and light–dark test (LD) in mice were used to determine AMPA/kainite receptor properties and anxiolytic-like activity of a series of 2,3BDZ-type compounds. Results The reference compound GYKI 52466 was proved active in two anxiety models in non-sedative doses: minimal effective dose (MED) was especially low in EPM (0.01 mg/kg) GYKI 53405 and GYKI 53655 showed anxiolytic-like activity in two tests (EPM and mCPP). EGIS-8332 was active in EPM and LD while EGIS-9637 showed anxiolytic-like potency in EPM, mCPP and Vogel model. EGIS-10608 was the most effective compound among 2,3BDZs tested in EPM and Vogel models (MEDs are 0.01 and 2.5 mg/kg, respectively). 2,3BDZs were active in anxiety models at doses lower than those produced sedative effects. NBQX showed anxiolytic-like activity in EPM only (3 mg/kg). Conclusions The results show that non-competitive AMPA receptor antagonists can profoundly block anxiety-like behavior in rodents independently from their motor depressant activity. However, the sedative properties at higher doses might limit their therapeutic utility as new anxiolytic drugs.     

松果菊苷对脑缺血大鼠纹状体细胞外液中氨基酸水平的影响

目的研究松果菊苷(ECH)对急性脑缺血大鼠纹状体细胞外液中4种氨基酸水平和脑梗死率的影响,以探讨ECH对脑神经保护作用的可能机制。方法 SD大鼠随机分为假手术对照组、模型组、阳性药川芎嗪组(CXQ,40 mg.kg-1)、ECH高剂量(ECH 40 mg.kg-1)组、ECH低剂量(ECH 20mg.kg-1)组和ECH配伍冰片(ECH 40 mg.kg-1,冰片400mg.kg-1)组。各组大鼠给予相应的药物或者生理盐水腹腔注射,每天1次,连续7 d。在给药d 3,脑纹状体埋置探针套管,末次给药1 h后,制作大鼠局灶性脑缺血模型(MCAO),模型成功后立刻进行微透析。将透析液注入高效液相-荧光检测器(HPLC-RF),此方法较氨基酸分析仪相比较,具有最低检测限低等特点,检测各组纹状体细胞外液中天门冬氨酸(Asp)、谷氨酸(Glu)、甘氨酸(Gly)、γ-氨基丁酸(GABA)的含量。结果与假手术对照组相比,模型组的Asp、Glu、Gly、GABA水平均明显升高;ECH给药组与模型组相比,ECH高剂量组能明显降低Asp、Glu的水平,而ECH低剂量组与ECH配伍冰片组Asp、Glu降低均不明显;ECH高、低组与配伍冰片组对Gly、GABA的影响均不明显;与模型组相比,ECH高、低剂量组能明显地缩小脑梗死面积。结论 ECH对脑神经的保护作用可能与对抗脑缺血后兴奋性氨基酸升高有关。     

注射用胡黄连总苷对ConA引起小鼠急性免疫性肝损伤的保护作用研究

目的利用Concanavalin A（ConA）引起的免疫性肝损伤模型,对注射用胡黄连总苷的保肝活性和量效关系进行研究。方法注射用胡黄连总苷静脉给予ICR小鼠（0．5—8mg·kg-1×5）,于末次给药后2h,动物尾静脉ConA20mg·kg-1,建立急性免疫性肝损伤模型,16h后处理动物,制备血清,全自动生化分析仪检测血清A1JT,AST及LDH水平,H.E．染色考察肝脏病理状态。结果ConA20mg·kg-1能引起小鼠显著的急性免疫性肝损伤,血清ALT,AST及LDH含量均显著升高,肝组织出现以炎症细胞浸润、肝细胞坏死为主要特征的病理改变。注射用胡黄连总昔0．5～Cmg·kg-1剂量对ConA引起的肝损伤有显著保护作用,明显降低血清转氨酶水平,改善肝脏病理状态,其中1mg·kg-1剂量药效最佳,8mg·kg。剂量药效有所下降,但此剂量未显示明显毒性。结论注射用胡黄连总苷对ConA引起的免疫性肝损伤有明确的保护作用,其起效剂量低,高于8mg·kg-1活性下降,在临床实验时需注意剂量的选择问题。