氯化二丁基锡对雄性小鼠睾丸和精子质量的影响

成年雄性小鼠腹腔注射 0 0 2 5～ 0 40 μg/kg/d氯化二丁基锡 (DBTCl) ,染毒 7d。实验温度 2 2± 2℃ ,光∶暗 =1 2h∶1 2h。结果表明 ,DBTCl对雄性小鼠生殖系统毒性影响很强。在≥ 0 0 5μg/kg剂量作用下 ,小鼠睾丸重量、精子存活率和密度明显下降 ,精子畸形率明显增加。观察发现 ,在 0 0 2 5～ 0 0 5μg/kg低剂量组中精子头部畸形率较高 ,而在0 2 0～ 0 40 μg/kg高剂量作用下 ,精子尾部的畸形率明显增加。剂量大于 0 1 0 μg/kg处理组小鼠体重明显下降。DBTCl和雄性小鼠生殖指标之间存在剂量 效应关系。DBTCl对精子存活率和精子密度 7d的ED50 值分别为 0 1 7和 0 1 9μg/kg。本项研究为有机锡化合物引起哺乳动物精子畸形的早期诊断提供可能的指标与方法     

灵芝发酵茶降低小鼠血清总胆固醇作用简报

报道灵芝发酵茶降低小鼠血清总胆固醇含量作用。试验采用BABL／c雄性小鼠,按体重随机分组,设高、中、低三个剂量和对照组,高、中、低三个剂量的试验组每天分别以4．198g／kg、3．358g/kg、2．798g/kg三个剂量灌服灵芝发酵茶提取液一次,对照组每天则以生理盐水灌服1次,连续给药10d,每天喂养高脂饲料。末次给药30min后,采用酶法测定小鼠血清总胆固醇含量。结果中剂量组试验小鼠血清总胆固醇含量和体重与对照相比分别降低了37．1％和7．7％。试验表明一定剂量的灵芝发酵茶对小鼠血清总胆固醇含量和体重的降低有显著作用。     

鹅膏菌中毒小鼠解毒药物的筛选

考察了几种中药对鳞柄白鹅膏中毒小鼠的解毒作用。鳞柄白鹅膏为极毒真菌,当其干燥子实体水溶液质量浓度>10mg/mL时,小鼠全部死亡,质量浓度为10mg/mL时,小鼠在9 h内全部死亡,选择这一浓度使小鼠中毒,使用所选中药对小鼠进行解毒试验。结果表明:水飞蓟(7.8 g/kg)、绿豆(3.9 g/kg)及甘草(1.3 g/kg)均能延迟小鼠的死亡时间,但与对照组相比差异不显著。灵芝(1.95 g/kg)对小鼠的死亡时间有明显的延迟作用,并与对照组相比差异显著(P<0.05)。同时使用灵芝剂量为首次解毒试验剂量的100倍水煎液(195 g/kg)和300倍水煎液(585 g/kg),以及按原料剂量为195 g/kg提取其中三萜及多糖用于对鹅膏中毒小鼠的解毒试验。结果表明:试验组小鼠的死亡时间均有延迟,其中195 g/kg剂量灵芝组和灵芝三萜试验组与对照组相比差异显著(P<0.05)。     

东莨菪碱镇痛作用的研究

腹腔(25或50mg/kg)或侧脑室注射东莨菪碱(1mg/kg),均使大鼠的痛阈升高42—80%,并持续32—36小时之久。当在恒温室内作昼夜连续观察时,对照组的大鼠在深夜20时至次日8时之前,痛刺激反应稍有增强,此时东莨菪碱组的镇痛作用也相应地减弱,而白天的镇痛作用较强,似有昼夜规律的表现。东莨菪碱的镇痛作用与脑内阿片能系统无关,DA 能暂时增强其镇痛作用,毒扁豆碱能拮抗其镇痛作用,所以,东莨菪碱的镇痛作用,主要是阻滞中枢 M-胆碱能系统的作用所致。     

灵芝孢子油长期毒性试验研究

目的:观察灵芝孢子油对大鼠产生的长期毒性反应和严重程度,确定本品安全用药剂量。方法:按1.67g/kg、0.83g/kg和0.42g/kg三个剂量,连续灌胃给药4个月及停药1个月,观察测试大鼠体重、血液学、血液生化学、脏器系数及病理组织学变化。结果:大鼠体重减轻,高剂量组ALP、TG值升高,高、中剂量组MCH、CREA值升高。结论:灵芝孢子油长期用药的安全剂量建议为每日用量不大于0.42g/kg。     

云芝、灵芝和柱状田头菇胞外多糖对果蝇寿命的影响

研究了云芝、灵芝、柱状田头菇等3种食药用真菌胞外多糖及复合多糖对黑腹果蝇寿命的影响.分别将3种食药用真菌胞外多糖及复合多糖以1、5g/L的剂量加入果蝇培养基中,观察对黑腹果蝇寿命的影响.结果表明,3种食药用真菌的胞外多糖及复合多糖对果蝇寿命均有不同程度的延长,云芝5g/L、柱状田头菇5g/L、云芝2.5g/L＋柱状田头菇2.5g/L、灵芝2.5g/L＋柱状田头菇2.5g/L对果蝇平均寿命延长率分别达到了36.38%、46.60%、36.69%、47.08%.     

金思维对东莨菪碱致记忆障碍小鼠脑胆碱能系统的影响

目的 通过建立东莨菪碱记忆障碍模型,采用中药复方金思维进行干预,观察金思维对东莨菪碱致记忆障碍模型小鼠行为学和胆碱能系统的影响,探讨该药的神经保护作用机制。方法 将ICR小鼠随机分为正常对照组;模型组,溶媒0.5%CMC;阳性对照组,多奈哌齐,0.92 mg/(kg·d);金思维大、中、小剂量组,20、10、5 mg/(kg·d)。每组18只,按0.1 mL/10 g小鼠体重连续灌胃给药30 d。末次给药后造模,对照组腹腔注射生理盐水,其余各组腹腔注射东莨菪碱3 mg/(kg·d),溶于0.9%生理盐水,按0.1 mL/10 g小鼠体重注射,进行Morris水迷宫实验。实验结束后取皮层和海马组织,分别测定皮层和海马中乙酰胆碱(Ach)含量、乙酰胆碱酯酶(Ach E)及胆碱乙酰转移酶(Ch AT)活性。结果 金思维可使模型小鼠游泳距离和游泳时间缩短及目标象限停留时间增长;金思维可使模型组小鼠脑内Ach含量升高、Ach E活性下降和Ch AT活性升高。结论 金思维可以改善东莨菪碱导致的记忆障碍模型小鼠学习记忆能力,其机制可能与胆碱能能系统有关。     

贯叶连翘提取物对小鼠抗应激反应及运动力竭小鼠抗氧化活性的影响

目的：研究贯叶连翘提取物（HPLE）对小鼠抗应激反应及运动力竭小鼠抗氧化活性的影响。方法：ICR小鼠,雌雄各半,随机均分为生理盐水（NS）对照组及高、中、低剂量HPLE组。分别采用负重游泳、常压耐缺氧和耐低温实验,观察小鼠抗急性应激反应能力,HPLE组分别按1.5 g/kg、0.75 g/kg和0.38 g/kg,ig,Bid,连续给药7 d;NS组等体积生理盐水ig。另取ICR小鼠40只,雌雄各半。随机均分为NS对照组及HPLE高、中、低剂量组。分别按ig HPLE 1.5 g/kg、0.75 g/kg和0.38 g/kg,q.d;对照组：ig等量NS,qd。连续用药2周后,开始每天进行游泳训练0.5 h,到第21天后,游泳力竭后休息20 min,断头取血,制备血清,检测小鼠血清中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性和丙二醛（MDA）的含量变化。结果：HPLE可延长小鼠负重游泳时间,缺氧存活时间及提高耐低温能力,并能升高运动力竭小鼠血清中SOD和GSH-Px活性,降低MDA的含量。结论：HPLE可提高小鼠应激反应能力,并具有抗氧化活性。     

灵芝酸枣仁胶囊改善睡眠的功能研究

为研究灵芝酸枣仁胶囊的改善睡眠功能,将ICR小鼠随机分为灵芝酸枣仁高、中、低剂量组和空白对照组,每组12只。人体推荐每公斤服用剂量为45 mg/kg·d,以此剂量的5倍、10倍和30倍,即每日以225 mg/kg BW、450 mg/kg BW和1 350 mg/kg BW经口灌胃30 d后,通过直接睡眠、延长戊巴比妥钠睡眠时间、巴比妥钠阈下剂量催眠和巴比妥钠睡眠潜伏期实验评价灵芝酸枣仁胶囊的改善睡眠作用。研究发现,与空白对照组相比,3个剂量组的直接睡眠实验结果皆为阴性(P0.05);与空白对照组相比,中剂量组小鼠延长戊巴比妥钠睡眠时间显著延长(P0.05),而高剂量组小鼠戊巴比妥钠睡眠时间极显著延长(P0.01);与空白对照组相比,高剂量组小鼠的入睡只数具有显著差异(P0.05),而睡眠潜伏期的小鼠只数具有极显著差异(P0.01)。研究表明,灵芝酸枣仁胶囊具有改善睡眠作用。     

5-氟尿嘧啶诱导小鼠化疗性肠黏膜炎模型的建立

目的研究5-氟尿嘧啶(5-fluorouracil,5-FU)诱导小鼠化疗性肠黏膜炎动物模型。方法采用不同剂量的5-FU单次或连续5 d腹腔注射给予小鼠,每日观察小鼠体重、腹泻情况,并分别于末次给药后72 h或24 h,观察小鼠外周血象及小肠组织病理形态学改变。结果与正常组比较,单次或连续5 d给予5-FU后,各剂量组小鼠出现不同程度的腹泻及体重降低,外周血象白细胞和血小板水平明显降低(P0.05或P0.01),其中单次给药400 mg/kg组、连续给药50,100 mg/kg组出现明显的肠黏膜炎病理特征,100 mg/kg组剂量过高,死亡率达100%。结论单次或连续5 d给予5-FU诱导小鼠肠黏膜炎的作用呈剂量相关性,其中单次给药以400 mg/kg为合适剂量,连续5 d给药以50 mg/kg为合适剂量。     

The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice

7-Oxo-dehydroepiandrosterone, which can be formed from dehydroepiandrosterone (DHEA) by several mammalian tissues, is more effective than its parent steroid as an inducer of thermogenic enzymes when administered to rats. Using the Morris water maze procedure, we tested DHEA and its 7-oxo-derivative for their ability to reverse the memory abolition induced by scopolamine in young C57BL/6 mice, and for their effect on memory in old mice. A single dose of 7-oxo-DHEA-acetate at 24 mg/kg b.w. completely reversed the impairment caused by 1 mg of scopolamine per kg b.w. (P < 0.001). DHEA (20 mg/kg) was also effective (P < 0.01). In old mice given the same single doses followed by feeding 0.05% of the respective steroid in the diet, memory of the water maze training was retained through a four week test period in mice receiving 7-oxo-DHEA-acetate (P < 0.05) but not in the control or DHEA-treated groups. When old mice were not tested until five weeks after being trained 7-oxo-DHEA exerted a slight, but statistically insignificant, improvement in memory retention. The possible effect of 7-oxo-DHEA in human memory problems deserves investigation.     

Holeboard discrimination learning in mice

We have adapted to mice a holeboard-learning task, which allows simultaneous assessment of spatial working and reference-memory performance. The holeboard apparatus consists of an open-field chamber with a 16-hole floor insert. Across trials, animals have to learn that the same four holes of 16 are always baited. Here, we show that C57BL/6 mice readily acquire this task within 4 days when submitted to six trials per day or within 8 days when submitted to only four trials per day. We also show that C57BL/6, Swiss-Webster, CD-1 and DBA/2 mice acquire this task similarly, despite the fact that some differences could be observed in measures of exploratory activity during habituation and training. Moreover, the muscarinic antagonist scopolamine disrupts learning at doses of 0.1 and 1.0 mg/kg, although the highest dose appeared to have side-effects. Lastly, we found that amyloid precursor protein transgenic mice have a selective disruption in their working-memory performance only during reversal training (i.e. after a change in the configuration of the baited holes). Overall, our data indicate that this spatial learning task is well adapted to mice and will be useful to characterize spatial memory in various genetic or pharmacological mouse models.     

Hyposensitivity to the amnesic effects of scopolamine or amyloid beta(25-35) peptide in heterozygous acetylcholinesterase knockout (AChE(+/-)) mice

We examined the sensitivity of AChE(+/-) mice to the amnesic effects of scopolamine and amyloid beta peptide. AChE(+/-) and AChE(+/+) littermates, tested at 5-9 weeks of age, failed to show any difference in locomotion, exploration and anxiety in the open-field test, or in-place learning in the water-maze. However, when treated with the muscarinic receptor antagonist scopolamine (0.5, 5mg/kg s.c.) 20min before each water-maze training session, learning impairments were observed at both doses in AChE(+/+) mice, but only at the highest dose in AChE(+/-) mice. The central injection of Abeta(25-35) peptide (9nmol) induced learning deficits only in AChE(+/+) but not in AChE(+/-) mice. Therefore, the hyper-activity of cholinergic systems in AChE(+/-) mice did not result in increased memory abilities, but prevented the deleterious effects of muscarinic blockade or amyloid toxicity.     

The influence of NMDA receptor agonist and antagonist on morphine state-dependent memory of passive avoidance in mice

The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. To explore the possible involvement of NMDA modulators on morphine-induced memory impairment, we have investigated the effects of intracerebroventricular (i.c.v.) administration of NMDA and the competitive NMDA antagonist, DL-AP5, on morphine-induced memory impairment or recall, on the test day. Morphine (5 mg/kg, s.c.) was administered 30 min before training to induce impairment of memory and 24 h later, 30 min before test to improve it. Pre-test administration of NMDA (0.00001, 0.0001 and 0.001 microg/mouse, i.c.v.) did not alter the retention latency compared to the saline-treated animals. But restored the memory impairment induced by pre-training morphine (5 mg/kg, s.c.). Pre-test administration of DL-AP5 (1, 3.2 and 10 microg/mouse, i.c.v.) by itself decreased the retention latencies. The same doses of DL-AP5 increased pre-training morphine-induced memory impairment. Co-administration of NMDA (0.0001 and 0.001 microg/mouse, i.c.v.) and morphine (5 mg/kg, s.c.) on the test day increased morphine memory improvement. Conversely, DL-AP5 (1, 3.2 and 10 microg/mouse, i.c.v.) inhibited morphine-induced memory recall. It is concluded that NMDA receptors may be involved, at least in part, in morphine state-dependent learning in mice.     

Dorsal hippocampal dopamine receptors are involved in mediating ethanol state-dependent memory

In the present study, the effects of bilateral injections of dopaminergic agents into the hippocampal CA1 regions (intra-CA1) on ethanol (EtOH) state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-peritoneal (i.p.) administration of EtOH (0.25, 0.5 and 1 g/kg) dose dependently induced impairment of memory retention. Pre-test administration of EtOH (0.5 g/kg)-induced state-dependent retrieval of the memory acquired under pre-training EtOH (0.5 g/kg) influence. Intra-CA1 administration of the dopamine D(1) receptor agonist, SKF 38393 (0.5, 1 and 2 g/mouse) or the dopamine D(2) receptor agonist, quinpirole (0.25, 0.5 and 1 microg/mouse) alone cannot affect memory retention. While, pre-test intra-CA1 injection of SKF 38393 (2 microg/mouse, intra-CA1) or quinpirole (0.25, 0.5 and 1 microg/mouse, intra-CA1) improved pre-training EtOH (0.5 g/kg)-induced retrieval impairment. Moreover, pre-test administration of SKF 38393 (0.5, 1 and 2 microg/mouse, intra-CA1) or quinpirole (0.5 and 1 microg/mouse, intra-CA1) with an ineffective dose of EtOH (0.25 g/kg) significantly restored the retrieval and induced EtOH state-dependent memory. Furthermore, pre-training injection of the dopamine D(1) receptor antagonist, SCH 23390 (4 microg/mouse), but not the dopamine D(2) receptor antagonist, sulpiride, into the CA1 regions suppressed the learning of a single-trial passive avoidance task. Pre-test intra-CA1 injection of SCH 23390 (2 and 4 microg/mouse, intra-CA1) or sulpiride (2.5 and 5 microg/mouse, intra-CA1) 5 min before the administration of EtOH (0.5 g/kg, i.p.) dose dependently inhibited EtOH state-dependent memory. These findings implicate the involvement of a dorsal hippocampal dopaminergic mechanism in EtOH state-dependent memory and also it can be concluded that there may be a cross-state dependency between EtOH and dopamine.     

Studies on anticonvulsant actions of L-deprenyl

L-Deprenyl (Selegeline) introduced for use in parkinson's disease, is implicated to show beneficial effects in epilepsy, alzheimer's disease, cognition, depression and other age related neurological diseases. In this study, we investigated the CNS effects of L-deprenyl with special reference to epilepsy, anxiety and cognition and memory in mice. L-deprenyl (10, 20 and 40 mg/kg) showed a significant anticonvulsant activity against pentylenetetrazole (PTZ)-induced convulsions. Combination of L-deprenyl (10 mg/kg) with the sub-protective dose of diazepam (1 mg/kg) showed potentiation of the anticonvulsant effect. In the maximal-electroshock (MES)-induced convulsions, L-deprenyl (10 mg/kg) significantly delayed the onset and decreased the duration of extensor phase. Its combination with the lower dose of phenytoin (10 mg/kg) showed potentiation in response compared to the per se effect of both the drugs. However, L-deprenyl did not show any protective effect in lithium-pilocarpine induced status epilepticus. Acute treatment with L-deprenyl had no effect on learning and memory. In chronic treatment, L-deprenyl per se showed no effect on learning and memory but did improve the condition in mice with scopolamine induced memory deficit. L-Deprenyl per se was anxiogenic though in combination with diazepam (1 mg/kg) it potentiated the antianxiety effect of the latter. The above observations suggest that in epilepsy, L-deprenyl might be acting partially by influencing the GABAA/benzodiazepine mechanism in the brain (similar to diazepam and phenytoin), and in cognition enhancing effect, the cholinergic system might be playing a role. Thus, L-deprenyl could prove to be an adjuvant in the antiepileptic therapy and beneficial in dementia associated with epilepsy.     

Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (brahmi), on experimental amnesia in mice

To investigate the effect of bacosides (alcoholic extract of brahmi) on scopolamine (3 mg kg(-1), ip), sodium nitrite (75 mg kg(-1), ip) and BN52021 (15 mg kg(-1), ip) induced experimental amnesia in mice, using Morris water maze test, all the agents were administered 30 min before the acquisition trials on each day and repeated for 4 consecutive days, and on 5th day during the retrieval trials. Bacosides on anterograde administration (before training) in mice, significantly decreased the escape latency time (ELT) during the acquisition trials for 4 consecutive days and increased the time spent (TS) in target quadrant during the retrieval trials on 5th day, and on retrograde administration (after training) bacosides were found not to affect TS significantly. Bacosides also significantly decreased the ELT and increased the TS in mice treated anterogradely with scopolamine and sodium nitrite. Bacosides did not exhibit any significant effect on TS of mice treated retrogradely with sodium nitrite. On the other hand, bacosides significantly increased the TS of mice treated retrogradely with BN52021. On the basis of the present results it can be concluded that bacosides facilitate anterograde memory and attenuate anterograde experimental amnesia induced by scopolamine and sodium nitrite possibly by improving acetylcholine level and hypoxic conditions, respectively. Beside this bacosides also reversed BN52021 induced retrograde amnesia, probably due to increase in platelet activating factor (PAF) synthesis by enhancing cerebral glutamate level.     

Effects of Scopolamine and Melatonin Cotreatment on Cognition,Neuronal Damage,and Neurogenesis in the Mouse Dentate Gyrus

It has been demonstrated that melatonin plays important roles in memory improvement and promotes neurogenesis in experimental animals. We examined effects of melatonin on cognitive deficits, neuronal damage, cell proliferation, neuroblast differentiation and neuronal maturation in the mouse dentate gyrus after cotreatment of scopolamine (anticholinergic agent) and melatonin. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally injected for 2 and/or 4 weeks to 8-week-old mice. Scopolamine treatment induced significant cognitive deficits 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly improved spatial learning and short-term memory impairments. Two and 4 weeks after scopolamine treatment, neurons were not damaged/dead in the dentate gyrus, in addition, no neuronal damage/death was shown after cotreatment of scopolamine and melatonin. Ki67 (a marker for cell proliferation)- and doublecortin (a marker for neuroblast differentiation)-positive cells were significantly decreased in the dentate gyrus 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly increased Ki67- and doublecortin-positive cells compared with scopolamine-treated group. However, double immunofluorescence for NeuN/BrdU, which indicates newly-generated mature neurons, did not show double-labeled cells (adult neurogenesis) in the dentate gyrus 2 and 4 weeks after cotreatment of scopolamine and melatonin. Our results suggest that melatonin treatment recovers scopolamine-induced spatial learning and short-term memory impairments and restores or increases scopolamine-induced decrease of cell proliferation and neuroblast differentiation, but does not lead to adult neurogenesis (maturation of neurons) in the mouse dentate gyrus following scopolamine treatment.     

A simple and reliable test of olfactory learning and memory in mice

The present paper describes a quick and efficient method for assessing olfactory discrimination learning in mice. In training mice received trials in which one odor (CS+) was paired with sugar and another odor (CS-) was paired with no sugar. When the mice were subsequently placed in a chamber with CS+ odor at one end and CS- odor at the other, they spent more time digging in CS+ than in CS- odor. In Experiment 2 mice trained with this procedure and tested after 60 days also spent more time digging in CS+ than CS- in the test phase, indicating that this olfactory discrimination task is effective for assessing long-term memory. In addition to the outbred strain of CD1 mice used in Experiments 1 and 2, C57Bl/6NCr/BR and DBA/2NCr/BR mice used in Experiment 3 also acquired this learned odor discrimination. Moreover, Experiment 4 showed that DBA animals were capable of acquiring this odor discrimination after receiving only two training trials (one exposure each to CS+ and CS-) per day for 4 days.     

钩藤散浸膏对小鼠记忆障碍模型的影响

目的观察钩藤散浸膏的益智作用。方法小鼠随机均分为6组,3个实验组每天灌胃高、中、低剂量的钩藤散浸膏,模型对照组与正常对照组每天灌胃蒸馏水(0.2 mL/10 g),阳性对照组每天给与茴拉西坦溶液(三乐喜,0.2 g生药/kg.bw),连续给药3周后,除正常对照组外,用东莨菪碱、亚硝酸钠、40%乙醇分别复制小鼠记忆获得障碍、记忆巩固障碍、记忆再现障碍模型,用Y型迷宫法测定小鼠训练和测试成绩。结果三种模型实验组的训练、测试成绩都显著好于模型对照组(P<0.01),记忆再现障碍模型的实验组测试成绩明显高于正常对照组(P<0.01)。结论钩藤散浸膏对各模型小鼠的记忆障碍皆有明显的改善作用,说明钩藤散浸膏有一定的益智作用。