加味酸枣仁颗粒镇静催眠作用实验研究

目的探讨加味酸枣仁颗粒的镇静、催眠作用。方法取SPF级昆明小鼠60只(雌雄各半),随机分为5组,每组12只,采用不同剂量加味酸枣仁颗粒对小鼠自发活动及戊巴比妥钠诱导小鼠睡眠潜伏期和睡眠时间进行镇静催眠试验研究。结果加味酸枣仁颗粒中、高剂量组较空白对照组小鼠自主活动次数显著减少,睡眠潜伏期显著缩短,睡眠时间显著延长(P<0.05或0.01)。结论加味酸枣仁颗粒具有明显的镇静、催眠作用。     

眠安方对小鼠镇静催眠作用的实验研究

目的观察眠安方灌胃给药后对小鼠的镇静催眠作用。方法采用阈上和阈下剂量戊巴比妥钠致小鼠睡眠的方法,观察眠安方不同剂量对小鼠自主活动及睡眠时间等影响。结果眠安方能明显减少小鼠自主活动次数,增加阈下剂量戊巴比妥钠致小鼠睡眠只数,改善阈上剂量戊巴比妥钠致小鼠睡眠时间。结论眠安方有明显的镇静催眠作用。     

益眠达片治疗失眠的药效学研究

目的观察益眠达片对小鼠的镇静催眠作用,观察小鼠对催眠及阈下催眠剂量戊巴比妥钠作用的影响,及益眠达片对小鼠自主活动的影响。方法实验小鼠随机分为:益眠达片高剂量组、中剂量组、低剂量组,安神补脑液组,艾司唑仑片组,空白对照组,按照实验要求给药,观察记录入睡潜伏期和睡眠持续时间,观察记录30min内翻正反射消失达1min以上的小鼠数以及末次给药30min后,2min内小鼠自发活动次数。结果益眠达片缩短戊巴比妥钠致小鼠入睡的潜伏时间,延长睡眠持续时间,增加阈下催眠剂量戊巴比妥钠小鼠入睡率;益眠达片可抑制小白鼠自发活动次数。结论益眠达片具有镇静催眠作用。     

酸枣仁汤对血虚小鼠的镇静催眠作用

目的:观察机体在血虚模型状况下,酸枣仁汤的镇静催眠作用。方法:①实验于2004-03/05在中国药科大学中医药教研室实验室完成。选用昆明种雄性小鼠246只。②观察酸枣仁汤(酸枣仁、甘草、知母、茯苓、川芎经煎煮制成酸枣仁汤颗粒。酸枣仁颗粒溶于蒸馏水,制成0.6,1.2,2.4g/mL溶液)对血虚小鼠戊巴比妥钠致睡眠时间的影响:取昆明种小鼠60只,随机分为5组:正常对照组、模型组(灌服生理盐水),酸枣仁汤低、中、高剂量组(灌服酸枣仁汤生药量6,12,24g/kg),每组12只。除正常对照组以外,其余各组造失血性贫血模型:小鼠眼眶放血0.5mL,24h后给药,连续给药5d,最后1d给药1h后,腹腔注射戊巴比妥钠35mg/kg。15min内翻正反射消失达30s以上为进入睡眠,翻正反射恢复为清醒,其间为睡眠时间,记录各组小鼠的睡眠潜伏期和睡眠期。③观察酸枣仁汤对血虚小鼠戊巴比妥钠阈下催眠剂量的影响:取昆明种小鼠66只,随机分成5组:正常对照组、模型组(n=12,21),酸枣仁汤低、中、高剂量组(n=11,12,10)。每组干预时间及干预措施同睡眠时间实验。分别腹腔注射戊巴比妥钠27mg/kg。腹腔注射后15min内翻正反射消失1min(睡眠)记为阳性(+),否则(清醒)记为阴性(-)。④观察酸枣仁汤对血虚小鼠自发活动的影响:每组小鼠只数、干预措施及干预时间同“睡眠时间”观察,进行旷野法实验:将小鼠放入直径30cm,高20cm的圆柱型笼中,笼底部分为19格,笼上方1m处放置60W白炽灯,描记小鼠在笼内2min的活动轨迹,轨迹与笼底格线相交记为1次。⑤观察酸枣仁汤对血虚小鼠血红蛋白的影响:每组小鼠只数、干预措施及干预时间同“睡眠时间”观察。用HiCN法测血红蛋白含量,给药第1天,第6天分别测血红蛋白含量,比较血红蛋白的变化值。⑥计数结果差异比较采用χ2Test孙氏直接概率法,组间计量结果比较采用t检验。结果:小鼠246只均进入结果分析。①酸枣仁汤低、高剂量组睡眠潜伏期明显短于模型组(P<0.01,0.05),睡眠期明显长于模型组(P<0.05)。②酸枣仁汤高、低剂量组睡眠小鼠只数明显多于模型组(P<0.05),清醒小鼠只数明显少于模型组(P<0.05)。③模型组小鼠自发活动次数明显少于对照组(P<0.01),酸枣仁汤中剂量组小鼠自发活动次数明显多于模型组(P<0.05)。④治疗前模型组小鼠血红蛋白含量明显低于对照组,治疗后酸枣仁汤中、高剂量组小鼠血红蛋白含量变化值明显高于模型组(P<0.05)。结论:①酸枣仁汤对机体在血虚小鼠具有镇静催眠作用。②酸枣仁汤能提高血虚小鼠血红蛋白含量,改善血虚症状,该作用具有剂量依赖性。     

夜交藤提取物对大鼠完全性脑缺血再灌注损伤保护作用的研究

目的研究夜交藤提取物对大鼠完全性脑缺血再灌注损伤的保护作用,并初步探讨其保护机制。方法取wistar大鼠,采用四血管阻断法制备完全性脑缺血再灌注损伤模型,将成模大鼠随机分为夜交藤组(灌胃给予夜交藤提取物)和模型组(灌胃生理盐水),另设假手术组(灌胃生理盐水),每组10只。再灌注72 h后,断头取血,比色法测血清一氧化氮合成酶(NOS)、超氧化物岐化酶(SOD)的活性及一氧化氮(NO)、丙二醛(MDA)的含量;取脑缺血组织,测定脑组织兴奋性氨基酸(EAA)含量。结果与模型组相比,夜交藤组大鼠血清SOD的活性升高,NOS的活性及NO、MDA含量均降低,能显著减轻缺血、缺氧造成的EAA含量增加,抑制EAA所导致的兴奋性神经毒性。结论夜交藤提取物对脑缺血再灌注损伤具有一定的保护作用,其保护机制与夜交藤提取物抑制NO释放及增强氧自由基的清除有关。     

植物油提取新工艺得到的五味子提取物对小鼠睡眠影响的实验研究

目的观察植物油提取新工艺得到的五味子提取物的改善睡眠作用。方法采用植物油提取新工艺得到五味子提取物,昆明种雄性小鼠随机分为对照组及五味子提取物低、中、高剂量组,对照组给予橄榄油20 ml/kg/d灌胃,五味子提取物低、中、高剂量组分别给予五味子提取物150、3006、00 mg/kg/d,连续灌胃15 d,通过直接睡眠实验、延长戊巴比妥钠睡眠时间实验、戊巴比妥钠阈下剂量催眠实验和巴比妥钠睡眠潜伏期实验,观察对小鼠直接睡眠、阈剂量戊巴比妥钠睡眠时间、戊巴比妥钠阈下剂量睡眠发生率及巴比妥钠诱导睡眠潜伏期的影响。结果采用植物油提取新工艺得到的五味子提取物可明显延长戊巴比妥钠诱导的小鼠睡眠时间,提高戊巴比妥钠诱导的小鼠睡眠发生率,缩短巴比妥钠诱导的小鼠睡眠潜伏期,对小鼠入睡动物数及睡眠时间均无明显影响。结论采用植物油提取新工艺得到的五味子提取物具有明显改善睡眠作用,有开发利用价值。     

酸枣仁汤对血虚小鼠的镇静催眠作用

目的：观察机体在血虚模型状况下，酸枣仁汤的镇静催眠作用。 方法：①实验于2004—03／05在中国药科大学中医药教研室实验室完成。选用昆明种雄性小鼠246只。（④观察酸枣仁汤（酸枣仁、甘草、知母、茯苓、川芎经煎煮制成酸枣仁汤颗粒。酸枣仁颗粒溶于蒸馏水，制成0．6，1．2，2．4g／mL溶液）对血虚小鼠戊巴比妥钠致睡眠时间的影响：取昆明种小鼠60只，随机分为5组：正常对照组、模型组（灌服生理盐水），酸枣仁汤低、中、高剂量组（灌服酸枣仁汤生药量6，12，24g／kg），每组12只。除正常对照组以外，其余各组造失血性贫血模型刊、鼠眼眶放血0．5mL，24h后给药，连续给药5d，最后1d给药1h后，腹腔注射戊巴比妥钠35mg／kg。15min内翻正反射消失达30s以上为进入睡眠，翻正反射恢复为清醒，其间为睡眠时间，记录各组小鼠的睡眠潜伏期和睡眠期。③观察酸枣仁汤对血虚小鼠戊巴比妥钠阈下催眠剂量的影响：取昆明种小鼠66只，随机分成5组：正常对照组、模型组（n=12，21），酸枣仁汤低、中、高剂量组（n=11，12，10）。每组干预时间及干预措施同睡眠时间实验。分别腹腔注射戊巴比妥钠27mg／kg。腹腔注射后15min内翻正反射消失1min（睡眠）记为阳性（＋），否则（清醒）记为阴性（-）。④观察酸枣仁汤对血虚小鼠自发活动的影响：每组小鼠只数、干预措施及干预时间同“睡眠时间”观察，进行旷野法实验：将小鼠放人直径30cm，高20cm的圆柱型笼中，笼底部分为19格，笼上方1m处放置60W白炽灯，描记小鼠在笼内2min的活动轨迹，轨迹与笼底格线相交记为1次。⑤观察酸枣仁汤对血虚小鼠血红蛋白的影响：每组小鼠只数、干预措施及干预时间同“睡眠时间”观察。用HiCN法测血红蛋白含量，给药第1天，第6天分别测血红蛋白含量，比较血红蛋白的变化值。⑥计数结果差异比较采用χ^2Test孙氏直接概率法，组间计量结果比较采用t检验。 结果：小鼠246只均进入结果分析。①酸枣仁汤低、高剂量组睡眠潜伏期明显短于模型组（P〈0.01，0．05），睡眠期明显长于模型组（P〈0．05）。②酸枣仁汤高、低剂量组睡眠小鼠只数明显多于模型组（P〈0．05），清醒小鼠只数明显少于模型组（P〈0．05）。③模型组小鼠自发活动次数明显少于对照组（P〈0．01），酸枣仁汤中剂量组小鼠自发活动次数明显多于模型组（P〈0．05）。④治疗前模型组小鼠血红蛋白含量明显低于对照组，治疗后酸枣仁汤中、高剂量组小鼠血红蛋白含量变化值明显高于模型组（P〈0．05）。 结论：①酸枣仁汤对机体在血虚小鼠具有镇静催眠作用。②酸枣仁汤能提高血虚小鼠血红蛋白含量，改善血虚症状，该作用具有剂量依赖性。     

脑力静胶囊的主要药效学研究

目的 :观察脑力静胶囊的主要药效学。方法 :采用镇静催眠 ,抗惊厥 ,自发活动和爬杆活动测定等方法。结果 :脑力静胶囊 (1 ,2 ,4g·kg- 1,ig ,qd× 7d)能延长戊巴比妥钠诱导的小鼠睡眠时间 ,对抗士的宁诱发的小鼠惊厥及抑制小鼠的自发活动 ,但对小鼠电休克惊厥发作及爬杆活动无明显影响。结论 :脑力静胶囊有一定的镇静催眠和抗惊厥作用。     

褐藻多糖的镇静催眠作用

目的:观察褐藻多糖对小鼠自发活动的影响,评价其抗惊厥,催眠和抗焦虑的作用。方法:①实验于2002-12/2003-05在南方医科大学药学院药理学教研室完成。选用健康成年昆明种小鼠250只,SD大鼠50只。②观察褐藻多糖对小鼠自发活动的影响:选取75只小鼠,随机分为5组:空白对照组(按0.1mL/10g的量灌胃蒸馏水),盐酸氯丙嗪组(在测试自发活动前30min按5mg/kg剂量腹腔注射盐酸氯丙嗪),低、中、高剂量褐藻多糖溶液组(分别按88.73,266.19,798.57mg/kg剂量灌胃褐藻多糖溶液),每组15只。给药2次/d,给药7d。采用YLS-1A多功能小鼠自主活动记录仪测定小鼠5min内自发活动次数。③观察褐藻多糖对小鼠催眠的影响:选取75只小鼠,分组及各组干预措施同“自发活动实验”。末次给药30min后腹腔注射戊巴比妥钠阈下催眠剂量30mg/kg,以翻正反射消失为指标,记录翻正反射消失的动物数。④观察褐藻多糖对小鼠惊厥的影响:取小鼠100只,随机分为5组:空白对照组,盐酸氯丙嗪组,低、中、高剂量褐藻多糖溶液组,每组20只。其中盐酸氯丙嗪组按1mg/kg剂量灌胃地西泮,其余各组分组及给药情况同“自发活动实验”。末次给药1h后按60mg/kg剂量腹腔注射5g/L戊四唑溶液,以出现阵发性抽搐为指标,观察每组发生惊厥的动物数。⑤观察褐藻多糖对大鼠焦虑的影响:应用大鼠Vogel冲突饮水实验模型。选取SD大鼠50只,随机分为5组:空白对照组(按1mL/100g的量灌胃蒸馏水),地西泮组(按1mg/kg剂量灌胃地西泮),低、中、高剂量褐藻多糖溶液组(分别按61.78,185.34,556.02mg/kg剂量灌胃褐藻多糖溶液),每组10只。2次/d,连续给药7d。实验分两阶段进行。大鼠禁水24h后进行无电击饮水训练(自发饮水训练),继续禁水24h再行饮水与电击结合实验(舔水与电击次数之比为20∶1),记录该期间大鼠舔水次数。⑥计量资料差异比较采用单因素方差分析,并用LSD法进行组间多重比较。计数结果差异比较采用χ2检验。结果:小鼠250只和大鼠50只均进入结果分析。①褐藻多糖对小鼠自发活动和戊巴比妥钠诱导的小鼠阈下睡眠的影响:中、高剂量褐藻多糖溶液组能明显减少小鼠的自发活动数,各剂量褐藻多糖溶液组能明显增强阈下剂量戊巴比妥钠诱导的小鼠翻正反射消失的作用,且该作用具有显著的剂量依赖性(P<0.01)。②褐藻多糖对戊四唑诱发的小鼠惊厥的影响:褐藻多糖连续给药7d,中剂量褐藻多糖溶液组能明显抑制戊四唑诱导的小鼠惊厥的作用,褐藻多糖对小鼠惊厥的抑制作用具有一定的剂量依赖性(P<0.05)。③褐藻多糖对大鼠焦虑的影响:褐藻多糖在较低剂量(61.78mg/kg和185.34mg/kg)时对大鼠的自发饮水次数无明显影响,只有在高剂量(556.02mg/kg)时增加大鼠的饮水次数,地西泮也在较高剂量(1.0mg/kg)时增加大鼠饮水次数。进一步的Vogel冲突实验显示,褐藻多糖在61.78,185.34和556.02mg/kg剂量下其抗焦虑作用呈现典型的钟型剂量-效应关系,有效剂量为185.34mg/g。结论:褐藻多糖有明显的镇静催眠、抗惊厥及抗焦虑的作用,且呈一定剂量依赖性,褐藻多糖的抗焦虑作用与地西泮类似。     

阿托品对氯胺酮小鼠催眠、镇痛、学习记忆的影响

目的:分析阿托品对氯胺酮小鼠催眠、镇痛、学习记忆的影响,以指导临床用药。方法:随机分小鼠80只为四组,每组各20只,各自使用相应方法,每组再划分NS组、At组、Ket组、At+Ket组,每组5只。各小组分别腹腔注射相关药物和生理盐水,并进行观察。结果:跳台与避暗的实验表明,阿托品不会影响小鼠的学习记忆。氯胺酮的镇痛作用比较明显(P0.05),阿托品则无以上作用。结论:阿托品对氯胺酮影响小鼠催眠、镇痛、学习记忆。氯胺酮短时间诱导,能够彻底镇静与镇痛,被用作分离麻醉剂;同时氯胺酮能增加呼吸道与唾液的分泌量,不能确保呼吸道的顺畅。阿托品是M胆碱受体阻滞剂,对腺体分泌起到阻碍作用。     

Osmotic minipumps for administration of barbital to mice: demonstration of functional tolerance and physical dependence

Sodium barbital was administered to mice at a constant rate by miniature osmotic pumps implanted subcutaneously. Each pump delivered approximately 0.25 mg/hr. With two pumps per mouse, blood barbital levels of 20 to 30 microgram/ml could be maintained for various periods. Barbital was assayed by gas chromatography. Functional tolerance was shown by a significant decrease in sleep time after a challenge dose of barbital administered 24 hours after withdrawal. Physical dependence was demonstrated by withdrawal hyperexcitability as measured either with pentylenetetrazol or by convulsions elicited by handling.     

玛咖对果蝇和小鼠繁殖能力与睡眠的影响

【目的】研究玛咖对果蝇和雄性小鼠性能力、繁殖能力以及睡眠的影响。【方法】用含有玛咖粉末（01．％,02．％）的培养基培养果蝇,检测玛咖对果蝇交配数以及羽化成虫数量的影响。进一步用玛咖混悬溶液按01．g／kg剂量和02．g／kg剂量给成年雄鼠连续灌胃15d,通过检测小鼠精液品质、观察其睾丸和附睾的组织学变化,并记录其子代生育情况,以评价小鼠的生殖力。通过直接睡眠动物数、戊巴比妥钠协同睡眠潜伏期、延长戊巴比妥钠睡眠时间以及戊巴比妥钠阈下剂量协同催眠动物数等指标来检测不同剂量组（01．g／kg ,02．g／kg和04．g／kg）玛咖对小鼠睡眠的影响。【结果】实验结果表明玛卡能显著提高果蝇的性交配率以及生殖率,增加并能明显增强小鼠睾丸的发育、提高精液品质,也能提升生育率和平均窝仔数以及子代平均体重和存活率。睡眠实验表明,玛咖不会引起实验动物直接睡眠,但能延长戊巴比妥钠诱导的睡眠时间,缩短其入睡潜伏期;在戊巴比妥钠阈下剂量催眠实验中能明显增加睡眠动物数。【结论】玛咖在不同的动物模型上都能提高雄性动物的性能力,增加其繁殖能力;并能改善动物睡眠。     

Deletion of the alpha1 or beta2 subunit of GABAA receptors reduces actions of alcohol and other drugs

Enhancement of the activation of GABAA receptors is a common feature of many sedative and hypnotic drugs, and it is probable that the GABAA receptor complex is a molecular target for these drugs in the mammalian central nervous system. We set out to elucidate the role of the two predominant (alpha1 and beta2) subunits of GABAA receptor in sedative drug action by studying mice lacking these two subunits. Both alpha1 (-/-) and beta2 (-/-) null mutant mice showed markedly decreased sleep time induced by nonselective benzodiazepine, flurazepam, and GABAA agonist, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol. The sleep time induced by the beta-selective drug etomidate was decreased only in beta2 (-/-) knockout mice. In contrast, alpha1 (-/-) mice were more resistant to the alpha1-selective drug zolpidem than beta2 (-/-) or wild-type animals. Knockout mice of both strains were similar to wild-type mice in their responses to pentobarbital. The duration of loss of the righting reflex produced by ethanol was decreased in male mice for both null alleles compared with wild-type mice, but there were no differences in ethanol-induced sleep time in mutant females. Deletion of either the alpha1 or beta2 subunits reduced the muscimol-stimulated 36Cl36 influx in cortical microsacs suggesting that these mutant mice have reduced number of functional brain GABAA receptors. Our results show that removal of either alpha1 or beta2 subunits of GABAA receptors produce strong and selective decreases in hypnotic effects of different drugs. Overall, these data confirm the crucial role of the GABAA receptor in mechanisms mediating sedative/hypnotic effects.     

Odour mechanisms: The psychological benefits of odours

There are many studies on the effects of odours and I have reviewed them in terms of both subjective psychological and objective pharmacological aspects.We measured a variety of odours from the relaxing lavender odour to the stimulating jasmine odour by examining contingent negative variation (CNV) which is a specific type of brain wave activity and is very sensitive to changes on effects. Although our results were in about 80% agreement with those of animal tests, further studies were needed to clarify the discrepancy between them. More detailed analysis of introspection of the subject after sniffing odours revealed that the changes of CNV magnitudes induced by odours were dependent upon the odour types perceived by the subjects. When we took these cognitive effects into account, our results were in a good agreement with those of the animal studies. Since the animal tests are aiming at the pharmacological effects of odorants, it can be quite possible that the pharmacological effects of odours may be in involved in some way in information processing occurring in olfactory perception.In parallel with the CNV series, we performed a study to assess the effects of the odour of lavender oil on the quality of sleep using all-night polygraphical recordings which allowed us to assess sleep architecture. We discovered that the odour of lavender had a definite beneficial effect on the quality of sleep, that is, more time was spent in both REM sleep and deep sleep. We believe such sleep-enhancing effect of the odour of lavender is mainly due to the objective pharmacological response. The idea that both the psychological and , the pharmacological effect intermingle with each other may help us to develop some guidelines for our rational and appropriate use of fragrance.     

Study on the hypnotic effect of rare protopanaxadiol-type and protopanaxatriol-type ginsenosides

Ginsenosides, as major active components of ginseng, possess various pharmacological activities, including anti-tumor, anti-diabetic and hypotensive effects. However, the sedative and hypnotic effect of ginsenosides and the involved mechanism remain unclear. In the present study, the hypnotic effect of rare protopanaxadiol-type (PD) ginsenosides, consisting of Rg3, Rk1, Rg5, and protopanaxatriol-type (PT) ginsenosides, consisting of Rh1, Rk3, Rh4, was investigated and compared in rodent models through behavioral pharmacology methods. Both rare PD and PT ginsenosides decreased spontaneous locomotion activity in normal mice and reduced sleep latency, and extended sleep duration in pentobarbital-treated mice. Moreover, PD and PT ginsenosides attenuated the insomnia induced by caffeine in mice. These hypnotic effects of PD and PT ginsenosides were potentiated by 5-hydroxytryptophan (5-HTP), a precursor of serotonin, and inhibited by p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. Flumazenil (FLU, a specific gamma aminobutyric acid (GABA) antagonist) also impaired the hypnotic effect of both PD and PT ginsenosides. The aforementioned results indicated that PD and PT ginsenosides exhibit sedative and hypnotic activity, and PT ginsenosides show higher activity than PD ginsenosides at high doses (96 mg kg⁻¹). Furthermore, the bioactivity of these two types of ginsenosides might be mediated via the serotonergic and GABAergic systems.

Ginsenosides, as major active components of ginseng, possess various pharmacological activities, including anti-tumor, anti-diabetic and hypotensive effects.     

青风藤和青藤碱在体外及体内对吗啡依赖模型纳洛酮催促戒断反应的影响

背景青风藤临床用于治疗阿片类戒断综合征有明显的疗效,但该药的作用及作用机制尚未明确.目的探讨中药青风藤及其有效成分青藤碱对吗啡依赖动物模型催促戒断反应的影响.设计完全随机对照实验研究.单位解放军第一军医大学中医系.对象体外实验研究对象为豚鼠离体回肠,分为正常回肠对照组,吗啡依赖回肠组,青风藤系列剂量组,青藤碱系列剂量组和尼莫地平组.体内实验研究对象为昆明种小鼠,共100只,雌雄各半,体质量18～24 g,随机分为正常对照组,吗啡依赖模型组,青风藤组,青藤碱组和丁丙诺啡组.干预体外实验,在吗啡依赖豚鼠回肠段的恒温浴槽中,预先加入青风藤醇提液(1,2,4g/L),青藤碱(10,50,150μmol/L)或尼莫地平(0.3μmol/L),1 min后再用纳洛酮催促.体内实验,对吗啡依赖小鼠分别给予青风藤醇提液(20 g/kg,灌胃),青藤碱(60 mg/kg,腹腔注射),丁丙诺啡(0.4 mg/kg,腹腔注射),或同体积生理盐水(腹腔注射),连续给药3 d,药后30min给予纳洛酮催促.豚鼠离体回肠实验采用PCLAB生物信号采集系统测定豚鼠回肠收缩张力变化.吗啡依赖小鼠催促戒断试验观察纳洛酮催促后30 min内各组小鼠跳跃反应的动物数及小鼠体质量的改变,连续观察4 d.主要观察指标①豚鼠回肠收缩张力.②小鼠跳跃反应的动物数.③大鼠体质量的变化.结果在离体豚鼠回肠实验中,纳洛酮催促引起的回肠收缩张力在正常对照组和吗啡模型组分别是(0.46±0.167),(2.11±0.566)g,差异有显著性意义(t=7.933,P＜0.01).青风藤3个剂量组的催促回肠收缩张力分别是(1.37±0.33),(0.85±0.271),(0.62±0.137)g,与吗啡模型组比较,差异有显著意义(t=3.203,5.701,7.268,P＜0.01).青藤碱3个剂量组的回肠收缩张力分别是(1.78±0.355),(1.28 ±0.233),(0.88±0.232)g,其中中、高剂量组与吗啡模型组比较,差异有显著意义(t=3.843,5.694,P＜0.01).在纳洛酮催促的吗啡依赖小鼠模型中,在实验的第7,8,9天(吗啡已撤退),吗啡模型组小鼠的跳跃只数最多,青风藤组和青藤碱组跳跃的动物较少.各组间差异有非常显著意义(x2=42.776,37.960,22.355,P=0.000).在给予吗啡造模的7 d中,小鼠体质量明显下降.撤离吗啡后,在第9,10天,小鼠体质量逐渐恢复并增加.与吗啡模型组相比,青风藤组和青藤碱组小鼠体质量恢复较快.在实验的第10天,丁丙诺啡组小鼠体质量较青风藤组和青藤碱组明显减少,差异有显著性意义(t=5.871,P＜0.01,t=2.819,P＜0.05).结论青风藤和青藤碱在体内外均能有效抑制吗啡依赖模型纳洛酮催促的戒断反应.     

Investigations into the mechanism of reduction of ethanol sleep by thyrotropin-releasing hormone (TRH).

Thyrotropin-releasing hormone (TRH), administered intraperitoneally, was found to antagonize ethanol-induced sleep and hypothermia in mice without affecting brain ethanol content. This reduction of the actions of ethanol was also apparent after oral or intracisternal administration of TRH. In addition, TRH reduced ethanol-induced sleep in rats, hamsters, gerbils and guinea pigs. Evidence that the pituitary-thyroid axis is not necessary for the effects of TRH was provided by observations that hypophysectomy did not reduce TRH antagonism of ethanol narcosis and findings that neither triiodothyronine nor thyrotropin mimicked its action. Certain analogs of TRH, which have little effect on the pituitary, were also found to antagonize ethanol-induced sleep and hypothermia. Pretreatment with the antiadrenergic drugs, alpha-methyltyrosine, phentolamine and propranolol did not antagonize the ability of TRH to reduce sleep induced by ethanol. However, after intracisternal administration of atropine methyl nitrate, TRH no longer caused a significant reduction of sleep, even though TRH antagonism of the ethanol-induced hypothermia was still apparent. In contrast, central administration of other anticholinergic drugs, such as delta-tobocurarine and hexamethonium, reduced ethanol-induced sleep and this effect was additive with TRH. Carbachol also reduced ethanol sleeping time and this effect was also blocked by atropine methyl nitrate. The antagonism of ethanol-induced sleep by dibutyryl cyclic adenosine 3', 5'-monophosphate was significantly reduced but not blocked by atropine methyl nitrate. Results provide evidence that TRH has a direct extrapituitary action on brain and that both TRH and ethanol may interact with central cholinergic systems.     

橙皮水提取物对昆明种小鼠睡眠和自发活动的影响

背景应用抖笼换能器法、阈上、阈下剂量戊巴比妥钠睡眠时间的实验法,探讨橙皮水提取物对昆明种小鼠睡眠和自发活动的影响.目的观察橙皮水提取物对昆明种小鼠睡眠和自发活动的影响.设计随机对照实验观察.单位赣南医学院病理教研室、生理学教研室及药理教研室.材料实验于2005-01/02在赣南医学院科研中心实验室完成.选择健康成年昆明种清洁级小鼠90只,每种实验方法30只,随机分为3组,对照组,小剂量给药组,大剂量给药组;每组10只.方法①采用抖笼换能器法记录小鼠自发活动情况,小波(波幅＜5 mm)为小鼠轻度活动(舐毛、瘙痒)的波形;中波(波幅5～10 mm)为小鼠中度活动(走动、立起、爬上、爬下)的波形;大波(波幅＞10 mm以上)为小鼠强度活动(跑动、上串下跳)的波形.小剂量给药组、大剂量给药组分别腹腔注射橙皮水提取物5 mg/g、10 mg/g和对照组注射等量生理盐水,15 min后放回吊笼中,稳定3 min后记录15s内小鼠活动波形.②橙皮水提取物对小鼠阈上或阈下剂量戊巴比妥钠睡眠时间的实验法小剂量给药组、大剂量给药组分别腹腔注射橙皮水提取物5 mg/g、10 mg/g,对照组注射等量生理盐水;15 min后,3组均腹腔注射阈上剂量的戊巴比妥钠(2.5g/L)0.02 mL/g,或阈下剂量的戊巴比妥钠(2.5 g/L)0.01 mL/g,比较给药组与对照组动物的入睡个数、入睡时间和睡眠持续时间.主要观察指标①小鼠自发活动次数.②阈上剂量戊巴比妥钠小鼠睡眠时间.③阈下剂量戊巴比妥钠小鼠睡眠时间.结果各实验组小鼠无脱失情况,全部进入结果分析.①橙皮水提取物小剂量给药组,大剂量给药组使中波、大波出现次数显著减少,对小鼠自发活动具有明显的抑制作用,[(90.5±14.7),(58.3±12.5),(45.6±10.1),t=2.341～3.215;P＜0.05或P＜0.01].②橙皮水提取物小剂量给药组,大剂量给药组能显著加速阈上剂量戊巴比妥钠的入睡时间和延长戊巴比妥钠的睡眠时间,差异有显著性意义.③橙皮水提取物小剂量给药组,大剂量给药组能显著加速阈下剂量戊巴比妥钠的入睡时间和延长戊巴比妥钠的睡眠时间,差异有非常显著性意义.结论橙皮水提取物具有明显的延长昆明种小鼠睡眠时间和抑制小鼠自发性活动.与戊巴比妥钠有协同的中枢抑制作用.