白芍总甙对大白鼠睡眠节律的影响

白芍总甙(TGP)每日ig 50mg·kg~(-1),连续7d可延长正常大鼠慢波睡眠(SWS)的持续时间.并能使咖啡因(12.5 mg·kg~(-1),ip)诱导的失眠大鼠睡眠各参数恢复到接近正常水平。TGP 50mg·kg~(-1)×3d)还可明显延长游泳大鼠(水温25±1℃.游泳时间30min)SWS和异相睡眠的总时间。上述实验结果提示TGP可改善不同功能状态下的大鼠睡眠。     

丙戊酸镁的抗躁狂作用

<正> 右旋苯丙胺,氯氮(艹卓)混合物(dexamphetamine chlordiazepoxide mixture,DCM)诱发的啮齿动物活动增多(hyperactivity)是一种较常用的躁狂症动物模型。在洞板法(holeboard)实验中,DCM组小鼠3min内的钻洞(head-dipping)次数为52±s11;用丙戊酸镁(magnesium valproate)预处理(75,150和300mg·kg~1,ig)的各组小鼠,其钻洞次数分别减少到40±s12,35±s11和32±s8.iv丙戊酸镁亦能剂量依赖性地阻止DCM所致小鼠活动增多,碳酸锂(lithium carbonate)预处理(75或150mg·kg~1ig,75mg·kg~1ip)也能     

双嘧达莫抗肿瘤作用的实验研究

给BALB/c和瑞士种实体瘤小鼠ig双嘧达莫(DIP)100、250和500mg·kg~(-1)·d~(-1)×10d.抑瘤率为34.20％～59.26％。ip DIP50和100mg·kg~(-1).对荷瘤C_(57)BL/6小鼠的抑瘤率分别为27.21％和52.18％;对瑞士种小鼠腹水中瘤细胞增殖抑制率为30.77％和48.92％.并能延长腹水瘤小鼠的存活时间。实验表明:DIP对小鼠S_(180)实体瘤和腹水瘤均有明显抑制作用。     

Kappa-晒化卡拉胶对实验动物的抗心律失常作用

Kappa-硒化卡拉胶是一含硒有机化合物。ip 9 mg·kg~(-1)·d~(-1)×5d或单次ig 35,70,140mg·kg~(-1)能显著提高乌头碱致大鼠HA的阈剂量,此作用可与Na_2SeO_3 1 mg·kg~(-1)·d~(-1)×5d ip比拟.随着Kappa-硒化卡拉胶ig剂量增加,尚可提高乌头碱所致VE,VT和VF的阈剂量。ip 9mg·kg~(-1)·d~(-1)×5 d或ig 70mg·kg~(-1)能提高BaCl_2致大鼠或哇巴因致豚鼠HA的阈剂量。对BaCl_2致大鼠VF或哇巴因致豚鼠VE的阈剂量,分别在ig70mg·kg~(-1)与140mg·kg~(-1)时有提高,而ipNa_2SeO_3 1 mg·kg~(-1)·d~(-1)×5d无此明显影响。     

新型抗精神病药奎的平副作用观察及护理

富马酸奎的平被称为平衡拮抗剂 ,不但对精神分裂症的阳性症状有效 ,对阴性症状亦有效 ,与氯氮平、利培酮、奥氮平一并被称为第四种新型非经典的抗精神病药物 ,于 2 0 0 0年被美国 FDA批准上市 ,国内今年初在临床上使用湖南洞庭制药厂生产的富马酸奎的平。本文小结我院今年 3～ 6月份应用该药 30例所出现副反应的观察与护理。1　资料与方法本组 30例均为住院女性病人 ,最小 2 2岁 ,最大 54岁 ,平均 34± 5.1 4岁。入院后测 BP、查三大常规、肝功能、生化、脑电图、心电图 ,并作 BPRS(简明精神病评定量表 )。入院后再做 PANSS(阳性和阴…     

国产尼美舒利的药效学研究

本文研究了国产尼美舒利在小鼠、大鼠及家兔体内的抗炎、镇痛和解热作用.结果表明.尼美舒利抑制巴豆油致小鼠耳廓肿胀(ED_(50)为49.2mg·kg~(-1));抑制角叉菜胶致大鼠足肿(ED_(50)为2.75mg·kg(-1));0.6mg·kg~(-1)剂量对大鼠佐剂关节炎有显著预防和治疗作用。100mg·kg~(-1)对小鼠醋酸扭体法的抑制率为68％;对热板法致痛的痛阈提高率为55％。ip给药对蛋白胨致家兔发热的解热作用.其最小有效剂量为2mg·kg~(-1);5mg·kg~(-1)ig可显著降低啤酒酵母致大鼠升高的体温.证实国产尼美舒利具有很强的抗炎、镇痛和解热作用。     

奎硫平及其代谢产物血药浓度与疗效、副作用的相关性

目的 探讨奎硫平及其代谢产物血药浓度与疗效、副作用的相关性。方法 对15例精神分裂症患者给予富马酸奎硫平治疗,剂量为400mg·d-1,疗程为3周。采用阳性症状量表(SAPS)、阴性症状量表(SANS)、简明精神病量表(BPRS)和不良反应量表(TESS)于治疗前和治疗1、2、3周末分别评定疗效和副作用。治疗第8 d晨服药前和服药后1.5 h分别采静脉血2 mL,高效液相色谱-质谱联用测定奎硫平及其代谢产物血药浓度。结果治疗结束时,SAPS、SANS和BPRS评分较治疗前均显著降低;BPRS减分率及SAPS减分率仅与奎硫平的稳态谷浓度均呈正相关;SANS减分率与峰、谷浓度均不相关。不良反应主要为一过性头昏和心动过速;TESS中的抗α1肾上腺素因子分值与奎硫平稳态峰浓度正相关,TESS总分值及其他因子分值与奎硫平及其代谢产物血药浓度不相关。结论 奎硫平治疗精神分裂症疗效好、起效快、耐受性好;监测奎硫平血药浓度对优化奎硫平临床疗效和预防药物不良反应具有重要意义。     

盐酸阿比朵尔安全性药理研究

目的:观察盐酸阿比朵尔对中枢神经系统、心血管系统和呼吸系统的影响。方法:观察ig给予盐酸阿比朵尔(10,50和250mg·kg~(-1))对小鼠大体行为、翻正反射、自主活动、感觉和记忆功能、睡眠诱导的影响;观察ig给予盐酸阿比朵尔(10,30和90mg·kg~(-1))对家兔体温变化的影响;观察ig给予盐酸阿比朵尔(20和80mg·kg~(-1))对麻醉犬的呼吸频率和幅度、收缩压和舒张压、心率及心律、心电图的QRS波、T波、ST段和PR间期的影响。结果:小鼠ig盐酸阿比朵尔(250mg·kg~(-1))有协同戊巴比妥钠睡眠诱导作用外,其余指标均无明显影响。结论:盐酸阿比朵尔对中枢神经系统、心血管系统和呼吸系统均无影响。     

国产头孢三嗪噻肟的体内抗菌作用研究

国产头孢三嗪噻肟对2株大肠杆菌感染小鼠的体内抗菌活性ED_(50)分别为0.0463mg·kg~(-1)和0.0386 mg·kg~(-1).与进口的头孢氨噻肟的ED_(50).0.0404mg·kg~(-1)和0.415mg·kg~(-1)相似.而比头孢三嗪噻肟的ED_(50)0.0617 mg·kg~(-1)和0.0561 mg·kg~(-1)低.国产头孢三嗪噻肟对2株克雷伯肺炎杆菌感染小鼠的体内抗菌活性ED_(50)为0.148 mg·kg~(-1)和0.147mg·kg~(-1).与进口的头孢三嗪噻肟的ED_(50)0.182mg·kg~(-1)和0.115 mg·kg(-1)相似.而比头孢氨噻肟的ED_(50)0.347 mg·kg~(-1)和0.799 mg·kg~(-1)明显的低.国产头孢三嗪噻肟对2株绿脓杆菌感染小鼠的体内抗菌活性ED_(50)24.579 mg.kg~(-1)和44.158 mg·kg~(-1)与进口头孢三嗪噻肟ED_(50)28.364 mg·kg~(-1)和34.818 mg·kg~(-1)相似.而比头孢氨噻肟ED_(50)>250和224.985 mg·kg~(-1)明显的低.对金黄色葡萄球菌感染小鼠的体内抗菌活性国产和进口头孢三嗪噻肟及头孢氨噻肟之间差异均没有显著性.     

复方氟尿嘧啶多相脂质体对S180荷瘤小鼠肿瘤生长抑制及其不良反应

目的:比较复方氟尿嘧啶多相脂质体(Co-5-FU)和氟尿嘧啶(5-FU)对小鼠肉瘤细胞系S180荷瘤小鼠的抗肿瘤作用及不良反应。方法:将小鼠肉瘤S180细胞悬液接种于小鼠背部皮下或腹腔,建立S180荷瘤小鼠实体瘤和腹水瘤模型。取70只小鼠,分成实验组(Co-5-FU)、阳性对照组(5-FU)和正常对照组,分别腹腔注射40 mg·kg~(-1)、20 mg·kg~(-1)、10 mg·kg~(-1)3种不同浓度的Co-5-FU和5-FU,正常对照组腹腔注射生理盐水。比较Co-5-FU和5-FU对实体瘤小鼠的肿瘤抑制率,腹水瘤小鼠的生命延长率,同时通过血生化和病理等检测观察2种药物对各脏器的不良反应。结果:与正常对照组比较,40 mg·kg~(-1)、20 mg·kg~(-1)、10 mg·kg~(-1) Co-5-FU对S180腹水瘤小鼠的生命延长率分别是52．7％,41．4％和31．9％(P＜0．05),对S180实体瘤小鼠的肿瘤抑制率分别是48．8％和39．2％和32．0％(P＜0．01);同等剂量Co-5-FU比5- FU引起的骨髓抑制轻(P＜0．05);40 mg·kg~(-1)5-FU可引起肝脏ALT、AST、GGP升高(P＜0．05)。结论: Co-5-FU比同等剂量的5-FU具有更强的抗肿瘤作用,对心脏、肾脏、肝脏、骨髓的不良反应明显小于5- FU。     

Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia.

1. Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces such negative symptoms in humans. 2. Repeated treatment with PCP (10 mg kg-1 day-1, s.c., once a day for 14 days) prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment; the effect was not obtained by single or 5 treatments with PCP (10 mg kg-1, s.c.), or by repeated treatment with methamphetamine (0.5 and 1 mg kg-1 day-1, s.c., once a day for 14 days). 3. The enhancing effect of PCP (10 mg kg-1 day-1, s.c.) on the immobility persisted for at least 21 days after the withdrawal of the drug. 4. Haloperidol (0.3 and 1 mg kg-1, p.o.), ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.1-1 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.) failed to attenuate the immobility induced by the forced swimming in mice repeatedly treated with saline when the drugs were administered 1 h before the forced swimming test. However, ritanserin (30 mg kg-1) and clozapine (30 mg kg-1) did attenuate this immobility. 5. The enhancing effect of PCP on the immobility was attenuated by ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.3 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.), whereas haloperidol (0.3 and 1 mg kg-1, p.o.) had no effect. 6. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5-HT2A receptors.     

菊淀粉型六聚糖对鼠强迫性游泳和低速率差式强化程序的影响

目的确定巴戟天中菊淀粉型六聚糖单体（ＩＨＳ）的抗抑郁作用。方法采用经典大小鼠强迫性游泳和程序化大鼠低速率差式强化（ＤＲＬ ７２ｓ）法。结果在小鼠强迫性游泳模型上,ｐｏ ＩＨＳ ８０ ｍｇ·ｋｇ－１与 ｉｐ地昔帕明 １０ ｍｇ·ｋｇ－１的作用类似,能明显缩短小鼠的不动时间;同样,ｐｏ ＩＨＳ ２０ｍｇ·ｋｇ－１也缩短大鼠强迫性游泳的不动时间,其效果与加地昔帕明 ４０ ｍｇ·ｋｇ－１相当。另外,在大鼠 ＤＲＬ ７２ｓ模型上,ｉｇ ＩＨＳ ５～１０ｍｇ·ｋｇ－ｌ和地昔帕明 ５ ｇ·ｋｇ－１,均增加大鼠ＤＲＬ－ ７２ｓ的强化数。结论 ＩＨＳ具有抗抑郁作用,是巴戟天中抗抑郁有效成分。     

Repeated phencyclidine treatment induces negative symptom-like behavior in forced swimming test in mice: imbalance of prefrontal serotonergic and dopaminergic functions.

Repeated treatment with phencyclidine (PCP) prolonged the immobility time in a forced swimming test, compared with saline treatment, this behavioral change being regarded as avolition which is one of the negative symptoms of schizophrenia. In the present study, we investigated an involvement of serotonergic (5-HTergic) and dopaminergic systems in PCP-induced enhancement of immobility in mice, since an alteration in 5-HTergic and dopaminergic systems has been hypothesized in schizophrenia. The enhancing effect of PCP on the immobility in a forced swimming test was attenuated by clozapine, risperidone and olanzapine, which have serotonin (5-HT) and dopamine receptor antagonistic properties. These attenuating effects were significantly antagonized by a 5-HT(2) receptor agonist, (+/-)-2,5-dimethoxy-4-iodamphetamine (DOI) without affecting the immobility itself. (-)Sulpiride at a low dose and methylphenidate reversed the PCP-induced enhancement of immobility whereas pimozide, chlorpromazine and levomepromazine had no effect. There was no difference in the frequency of DOI-induced head twitches, which are mediated via 5-HT(2) receptors, between PCP- and saline-treated mice following the forced swimming test, indicating no functional changes in post-synaptic 5-HT(2) receptors. 5-HT utilization in the prefrontal cortex was increased, but dopamine utilization was decreased in mice showing PCP-induced enhancement of immobility. These results suggest that the enhanced effect of PCP on the immobility is mediated by imbalance of 5-HTergic and dopaminergic systems in the prefrontal cortex and could be used as a model of the negative symptoms of schizophrenia.     

丹参酮的抗抑郁作用研究

目的：研究丹参酮的抗抑郁作用。方法：丹参酮灌胃给药。通过尾静脉注射利血平（2mg·kg-1）复制小鼠抑郁模型,观察眼帘下垂动物数、运动不能动物数,测肛温;腹腔注射丁苯那嗪（40mg·kg-1）复制小鼠抑郁模型,观察眼帘下垂动物数和僵住动物数;尾静脉注射利血平（2mg·kg-1）后进行悬尾、强迫游泳实验,复制小鼠获得性绝望模型,观察小鼠悬尾不动时间和游泳不动时间;通过静脉注射单胺氧化酶抑制剂（盐酸色胺）复制大鼠惊厥模型,观察大鼠动作平均分值、拍打动作持续时间。结果：60、30、20mg·kg-1丹参酮可显著减少利血平复制的抑郁模型小鼠眼帘下垂、运动不能动物数,显著升高模型小鼠肛温（P〈0.05）;60、30mg·kg-1丹参酮可显著减少丁苯那嗪复制的抑郁模型小鼠眼帘下垂、僵住动物数（P〈0.01或P〈0.05）;60、30mg·kg-1丹参酮可显著缩短绝望模型小鼠悬尾不动、游泳不动时间（P〈0.01）;42、21、14mg·kg-1丹参酮可显著降低盐酸色胺复制的惊厥模型大鼠动作平均分,42、21mg·kg-1丹参酮可显著缩短模型大鼠拍打动作持续时间（P〈0.01或P〈0.05）。结论：丹参酮有一定抗抑郁作用。     

The paw test: a behavioural paradigm for differentiating between classical and atypical neuroleptic drugs

An often used animal model based on the effects of neuroleptics on spontaneous behaviour is the catalepsy test. However, this test seems to be particularly insensitive to the atypical neuroleptics thioridazine and, especially, clozapine. We have therefore developed an alternative test, the paw test, which measures the ability of drugs to prevent the spontaneous withdrawal of fore- and hindlimbs in rats, and have compared this with the classical catalepsy test. The results show that: 1) the classical neuroleptic drugs haloperidol and chlorpromazine, the atypical neuroleptic drugs clozapine and thioridazine, the potential atypical neuroleptic drugs molindone and SCH 23390, and the potential classical neuroleptic drug metoclopramide are potent in increasing the hindlimb retraction time; 2) the paw test discriminates between classical neuroleptics which are equipotent in prolonging both the forelimb (FRT) and hindlimb retraction time (HRT) and atypical neuroleptics which are much more potent in prolonging HRT than in prolonging FRT; 3) the non-neuroleptic drugs desipramine, diazepam and morphine do not influence the variables measured in the paw test, although morphine does produce catalepsy; 4) Molindone as well as SCH 23390 behave like atypical neuroleptic drugs in the paw test. In comparison with the classical wood block catalepsy test, the paw test is shown to be superior for predicting the profile of the neuroleptics tested. Although more neuroleptics and non-neuroleptics have to be tested to determine whether false positives and false negatives do occur, we feel that the paw test might be an interesting animal model, because the increase in hindlimb retraction time was associated with the antipsychotic potential, whereas the increase in forelimb retraction time was associated with the potential to induce so-called extrapyramidal side effects.     

小补心汤总黄酮对强迫游泳和获得性无助模型动物的抗抑郁作用(英文)

目的小补心汤(XBXT)由代赭石、旋覆花、竹叶和淡豆豉4味中药组成,文献记载其有缓解抑郁情绪的作用。本实验研究其总黄酮提取物(XBXT-2)是否具有抗抑郁作用。方法采用大、小鼠强迫游泳模型和大鼠获得性无助模型观察XBXT-2的抗抑郁作用,采用酶联免疫法检测获得性无助大鼠血清皮质酮水平,并观察XBXT-2对小鼠自发活动的影响。结果单次灌胃给予XBXT-2 50和100mg.kg-1可以显著缩短小鼠和大鼠强迫游泳的不动时间。连续4 d灌胃给予XBXT-2 25和50 mg.kg-1可以显著减少获得性无助模型大鼠的逃避失败次数,并显著降低其血清皮质酮水平。XBXT-2 50 ～200 mg.kg-1对正常小鼠的自发活动性无明显影响。结论 XBXT-2在抑郁动物模型上具有抗抑郁样作用,其机制可能与其抑制下丘脑-垂体-肾上腺轴功能亢进有关。     

Neuropsychopharmacological study on an animal model for negative symptom of schizophrenia induced by repeated phencyclidine treatment

To develop an animal model for negative symptoms, in particular avolition, of schizophrenia, the effect of phencyclidine (PCP) on immobility (regarded as avolition) in the forced swimming test was investigated in mice, since PCP produces negative symptoms in humans. Unlike single, repeated treatment with PCP prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment. The enhancing effect of PCP on the immobility persisted for 21 d after the withdrawal of the drug. Atypical antipsychotics attenuated the enhancing effect of PCP on the immobility. Since these attenuating effects were antagonized by a serotonin-S2 receptor agonist, (+/-)-2,5-dimethoxy-4-iodamphetamine (DOI), the effects may be mediated via serotonin-S2 receptors. In contrast with atypical antipsychotics, typical antipsychotics, antidepressants and anxiolytics had no effect. No functional changes in post-synaptic serotonin-S2 receptors were observed in PCP-treated mice following the forced swimming test. Serotonin utilization in the prefrontal cortex was increased, but dopamine utilization was decreased in PCP-treated mice showing the enhancement of immobility. The enhancing effect of PCP was significantly attenuated by D-cycloserine, an agonist for glycine binding site of N-methyl-D-aspartate (NMDA) receptor ionophore complex. Decreases of NMDA receptor function or of the cortical glutamate and glycine levels were observed in PCP-treated mice showing the enhancement of immobility. These results suggest that the enhancing effect of PCP on immobility is mediated by the imbalance of the cortical serotonergic, dopaminergic and glutamatergic systems and could be used as an animal model for negative symptoms of schizophrenia.     

精神分裂症患者富马酸喹硫平血浓度测定及血浓度疗效关系

目的建立反相高效液相色谱法测定精神分裂症患者富马酸喹硫平血浓度的方法学,探讨其血浓度与患者年龄、性别、服药剂量及临床疗效的关系.方法采用高效液相色谱法测定76例单一服用富马酸喹硫平的精神分裂症住院患者治疗前及治疗后第2、4、6 wk 肘静脉血浓度,并进行BPRS量表评定及相关性分析.结果富马酸喹硫平血浓度在 0.05～0.5 mg*L-1范围内有良好线性关系(r=0.9850).日剂量50～450 mg 时血浓度随剂量增大而升高,但与服药患者年龄、性别无显著相关性.血浓度在 0.126～0.350 mg*L-1范围内临床效果较好.结论测定方法简便、准确、专一性强,可用于富马酸喹硫平治疗药物监测.治疗窗浓度为 0.126～0.350 mg*L-1.     

咖啡酸对慢性应激大鼠的抗抑郁作用

目的探讨咖啡酸对慢性应激大鼠的抗抑郁作用。方法采用各种慢性不可预见轻微刺激建立大鼠抑郁模型。21 d后,ig给予大鼠咖啡酸10,30和50 mg.kg-1,连续21 d。通过旷场实验检测中央格停留时间、水平活动和垂直活动情况,通过强迫游泳实验检测大鼠静止不动行为百分比(PI);检测海马超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量。结果与正常对照组相比,模型组大鼠在旷场实验中央格停留时间增长,水平活动和垂直活动减少,强迫游泳静止不动状态增加,SOD活性显著降低,MDA含量显著升高(P<0.01)。与模型组相比,咖啡酸10～50 mg.kg-1组能够显著缩短停留时间(P<0.05)、增加垂直活动(P<0.01),但对水平活动无明显影响。模型组PI为(79.69±15.84)%,咖啡酸10～50 mg.kg-1组PI显著降低,分别为(16.00±2.11)%,(10.33±2.92)%和(7.33±2.63)%。与正常对照组相比,模型组SOD酶活性显著降低,MDA含量显著增加(P<0.01),与模型组相比,咖啡酸10～50 mg.kg-1能够显著增加SOD酶活性,分别为模型组的1.50,2.46和2.59倍(r=0.915,P<0.01);MDA含量显著降低,分别为模型组的18.64%,11.37%和6.35%(P<0.01),且呈剂量依赖性(r=0.982,P<0.01)。咖啡酸与舍曲林5 mg.kg-1的作用相似。结论咖啡酸对慢性应激大鼠有一定的抗抑郁作用。     

吗氯贝胺在鼠强迫游泳行为实验中的抗抑郁效应

用大鼠和小鼠强迫游泳行为模型观察了吗氯贝胺的抗抑郁效应。大鼠一次给予吗氯贝胺１０－１００ｍｇ·ｋｇ￣（－１）无影响。２４ｈ内３次强化给药使游泳不动时间减少。若每日给药２次。连续１５次则不但效应进一步加强且呈较好的量效关系，同时活动性不增加。小鼠单次或３次强化给予吗氯贝胺对游泳不动时间均无明显影响。每日１次。连续给药２０ｄ，表现出与大鼠同样的良好效应和量效关系。活动性亦无增高。