滇产粗根荨麻不同提取部位的镇痛抗炎作用研究

为探讨滇产粗根荨麻不同部位的镇痛抗炎活性,并作有效部位筛选,本文采用醋酸扭体法和角叉菜胶致大鼠足肿胀模型筛选有效部位.正丁醇部分(200 mg/kg)对醋酸诱发小鼠扭体有抑制作用与空白及溶媒对照组比较(P＜0.05);水部分(100,200,400 mg/kg)对角叉菜胶致大鼠足肿胀有明显抑制作用,与空白及溶媒对照组比较(P＜0.01);正丁醇部分(400 mg/kg)可减轻角叉菜胶致大鼠足肿胀,与空白及溶媒对照组比较(P＜0.05).滇产粗根荨麻正丁醇部分有一定的镇痛抗炎作用,水部分具较强抗炎作用.     

消栓通胶囊抗脑缺血作用的实验研究

目的:观察消栓通胶囊对双侧颈总动脉结扎的大鼠脑缺血的保护作用;对小鼠断头后存活时间的影响.方法:采用结扎大鼠双侧颈总动脉以造成脑缺血模型,观察消栓通胶囊的药理作用.结果:①a.消栓通胶囊对双侧颈总动脉结扎大鼠脑含水量及脑指数有显著影响,消栓通胶囊三个剂量组(0.20 g/kg、0.40 g/kg、0.80 g/kg),脑含水量明显减少,与模型组有显著差异(P＜0.05或P＜0.01).b.组织病理学检查表明消栓通胶囊组的脑组织神经细胞浓缩及深染较脑缺血模型组明显减轻;神经胶质细胞肿胀及间质疏松程度均明显轻于模型组.②消栓通胶囊三个剂量组(0.20 g/kg、0.40 g/kg、0.80 g/kg)均能明显降低全血粘度值,与模型组比较有明显差异(P＜0.05或P＜0.01);③消栓通胶囊三个剂量组(025g/kg、0.50g/kg、1.00 g/kg)给药14d,与正常组比较可延长小鼠断头喘气的时间(P＜0.05或P＜0.01).结论:消栓通胶囊对大鼠结扎双侧颈总动脉所致脑缺血损伤具有明显的保护作用.     

过量人参皂苷对小鼠脑组织谷氨酸代谢的影响

目的:探讨过量人参皂苷对小鼠脑组织中谷氨酸代谢的影响。方法:常规饲养昆明小鼠,按照最终浓度低(8 mg/kg)、中(40mg/kg)、高(200 mg/kg)剂量连续灌胃人参皂苷24天,记录小鼠体重变化。第25天颈脱臼处死小鼠,取出全脑匀浆后测定谷氨酸水平,谷氨酰胺酶活力。结果:各实验组与对照组相比,体重明显下降;低、中、高实验组谷氨酸水平分别高与对照组13.66%、21.67%、39.83%,其中中剂量组和高剂量组显著高于空白组(P0.05);谷氨酰胺酶活力较对照组分别增高2.06%、2.91%、10.11%,高剂量与空白组差异显著,有统计学意义(P0.05)。结论:高剂量人参皂苷能使神经系统兴奋,可能与增高谷氨酰胺酶活力、从而提高脑组织中谷氨酸含量有关。     

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。     

胆囊收缩素受体拮抗剂加强大鼠的吗啡镇痛和羟甲芬太尼镇痛

已知大鼠脊髓蛛网膜下腔(i.t.)注射CCK-8能拮抗阿片μ受体介导的镇痛作用。本文给大鼠i.t.注射高选择性CCK-A受体拮抗剂devazepide和CCK-B受体拮抗剂L-365260阻断内源性释放的CCK-8,观察对阿片镇痛的影响。i.t.注射100ng devazepide或2.5ng L-365260可显著地增强吗啡镇痛(4mg/kg,sc),两者的剂量效应曲线均为钟形曲线;i.t.注射66ng devazepide或1.25ng L-365260也能显著地增强羟甲芬太尼(专一的阿片μ受体激动剂,OMF)的镇痛作用(32ng,i.t.),剂量效应曲线亦为钟形曲线。这两种CCK受体拮抗剂本身对病阈无影响。 以上结果表明,脊髓内有内源性CCK-8发挥对抗阿片镇痛作用;鉴于devazepide剂量大于L-365260剂量40-50倍,提示CCK-8在脊髓的抗阿片镇痛功能是通过CCK-B受体实现的。     

不同浓度沙利度胺对大鼠慢性坐骨神经缩窄模型的镇痛效果及机制

目的:比较不同剂量沙利度胺对大鼠慢性坐骨神经缩窄(chronic sciatic nerve constriction,CCI)的镇痛效果及可能机制。方法:将50只大鼠随机分为S组、C组、L组、M组及H组,S组作为假手术组,其余四组建立CCI模型,术后分别用20 mg/kg、50mg/kg、100 mg/kg沙利度胺处理L组、M组、H组。于术后第1、2、3、4周测量和比较各组大鼠机械性痛阈与热痛阈,采用蛋白质印迹法(Western blot)及实时荧光定量PCR(Q-PCR)检测各组大鼠肿瘤坏死因子受体(TNFR)的mRNA和蛋白表达,并分析沙利度胺浓度与TNFR mRNA相对表达的相关性。结果:S组术前术后的机械性痛阈与热痛阈均无明显改变(P0.05),其余四组术后痛阈均较术前明显下降(P0.05);C组术后第4周时机械性痛阈明显升高(P0.05),而术后其他时间点的机械性痛阈与热痛阈无明显差异(P0.05);L组、M组、H组术后机械性痛阈、热痛阈随时间的延长呈上升趋势,差异有统计学意义(P0.05)。术后,C组机械性痛阈与热痛阈对比S组明显降低(P=0.000),亦显著低于L组(P=0.000);而不同剂量组机械性痛阈、热痛阈相比,H组高于M组(P=0.000),M组高于L组(P=0.000)。相对于C组,L组、M组、H组术后第4周TNFR1 mRNA及蛋白相对含量显著下降(P0.05),其中H组下降最为明显,M组次之。Pearson相关性分析结果显示:沙利度胺浓度的增加与TNFR1表达水平的升高呈明显负相关关系(r=-0.497,P=0.036)。结论:沙利度胺可能通过影响TNFR表达水平对大鼠慢性坐骨神经缩窄发挥镇痛效应,其镇痛效应随剂量增加而加强,有望作为神经病理性疼痛的辅助镇痛药物之一。     

克班宁的镇痛作用部位及作用机制探讨

以探究克班宁的镇痛作用部位并初步明确其镇痛机制为目的。采用小鼠足趾注射甲醛法、热板法及腹腔注射醋酸(扭体法)所致疼痛模型,探讨克班宁的镇痛作用;以小鼠输精管经壁电刺激法,了解克班宁对吗啡受体的影响。结果发现克班宁在3.2 mg/kg时对三种疼痛模型均显示明显的抑制作用,并能明显抑制小鼠输精管经壁电刺激所引起的收缩,且该收缩不能被纳络酮所拮抗。因此,克班宁可能具有中枢样镇痛作用,但作用机制与吗啡受体无关。     

阴虚动风证帕金森病异动症大鼠大麻素CB1受体变化及复方地黄方的干预作用

目的探讨阴虚动风证帕金森病(PD)异动症(LID)大鼠纹状体内大麻素CB1受体的表达及复方地黄方的干预作用。方法采用6-羟基多巴胺(6-OHDA)偏侧损毁黑质制备帕金森病大鼠模型,进一步腹腔注射左旋多巴+苄丝肼(50 mg/kg左旋多巴和12.5 mg/kg苄丝肼)制备LID大鼠模型,并随机分为LID组、复方地黄方组,另取正常对照组、假手术组大鼠为对照,每组6只。分别在4周、6周进行神经行为学检测后,处死大鼠并取纹状体,应用Western blot法测定各组大鼠纹状体内大麻素CB1受体的表达情况。结果 LID大鼠随造模时间延长,AIM评分呈增加趋势(P0.05),旋转启动时间呈缩短趋势(P0.05),旋转持续时间呈增加趋势(P0.01),剂峰旋转圈数呈减少趋势(P0.05),复方地黄方可改善上述变化。LID大鼠大麻素CB1受体表达增加,且随造模时间延长呈现减少趋势(P0.01),而复方地黄方干预后大麻素CB1受体的表达呈现逐渐增加的趋势(P0.01)。结论LID模型大鼠大麻素CB1受体的含量明显升高,其变化能够较好的反映阴虚动风证的严重程度,复方地黄方干预LID模型大鼠可能是通过激活纹状体内大麻素CB1受体,抑制兴奋性氨基酸(主要是谷氨酸)的释放和诱导细胞发生级联反应来减弱神经元的兴奋性,从而起到减轻L-dopa的兴奋毒性的作用。     

中风胶囊对脑缺血/再灌注损伤模型鼠脑组织自噬相关蛋白表达的影响*

目的: 观察中风胶囊对脑缺血/再灌注损伤(CIRI)模型鼠脑组织自噬相关蛋白表达的影响,初步揭示其对神经元损伤保护的分子机制。方法: 采用改良线栓法构建大鼠脑缺血/再灌注损伤模型,随机将60只雄性SD大鼠分为假手术组、模型组、丁苯酞组(0.054 g/kg)、中风胶囊高剂量组(1.08 g/kg)、中风胶囊中剂量组(0.54 g/kg)、中风胶囊低剂量组(0.27 g/kg),每组10只。造模结束后灌胃给药10 d,每天1次,实验结束后处死各组大鼠,摘取脑组织。各组大鼠末次给药24 h后进行神经功能评分;HE染色法观察各组大鼠脑组织病理形态;ELISA法检测各组大鼠血清雌二醇(E2)和卵泡刺激素(FSH);RT-PCR法与Western blot法分别测定各组大鼠脑组织PI3K/Akt/Beclin1信号通路关键基因及蛋白的表达。结果: 与假手术组比较,模型组大鼠体重及脑组织中p-PI3K、p-Akt等蛋白表达均显著降低,脑指数、神经功能缺损评分及脑组织Beclin1、LC3基因和蛋白表达均显著升高(P＜0.05或P＜0.01),脑组织结构排列疏松,间质水肿,神经细胞呈三角形,核固缩深染。与模型组相比,中风胶囊高剂量组大鼠体重显著升高,神经功能缺损评分显著下降(P＜0.05),脑组织病理损伤较模型组明显改善;中风胶囊各剂量组的脑指数及脑组织Beclin1、LC3的基因和蛋白表达均显著降低,脑组织中p-PI3K、p-Akt等蛋白表达均显著升高(P＜0.05或P＜0.01)。结论: 中风胶囊通过调控PI3K/Akt/Beclin1信号通路中Beclin1和LC3的表达来抑制CIRI模型鼠的自噬反应,从而发挥保护其脑神经元损伤的作用。     

欧前胡素对Aβ_(1-42)致阿尔茨海默病小鼠学习记忆障碍的影响

研究欧前胡素(imperatorin,Imp)对Aβ_(1-42)致阿尔茨海默病(Alzheimer’s disease,AD)小鼠学习记忆的影响及机制。小鼠脑室内注射Aβ_(1-42)制备AD模型,Imp 2.5 mg/kg和5.0 mg/kg在手术后当天开始腹腔注射给药,1次/d,连续给药13 d,正常对照组和模型组在相同的给药时间点给予溶媒0.1 mL/10 g。第14 d,采用跳台法观察小鼠的学习记忆功能,检测小鼠脑组织内活性氧簇(reactive oxygen species,ROS)、脂质过氧化产物丙二醛(malondialdehyde,MDA)和总抗氧化能力(Total antioxidant capacity,T-AOC)及ATP酶活性。研究显示,同AD模型组比较,Imp 2.5 mg/kg和5.0 mg/kg组小鼠的跳台潜伏期明显延长(P0.05,P0.01)和错误次数明显减少(P0.05,P0.01),Imp 2.5 mg/kg和5.0 mg/kg组小鼠脑组织中ROS和MDA含量明显降低(P0.05,P0.01),Imp 5.0 mg/kg组T-AOC明显增强(P0.01),Imp 2.5 mg/kg和5.0 mg/kg组Na~+、K~+-ATP与Ca~(2+)-ATP酶的活性明显增强(P0.05,P0.01)。研究结果提示,Imp可能通过抑制AD小鼠脑组织中氧化应激损伤,从而改善Aβ_(1-42)致AD小鼠的学习记忆功能。     

Involvement of NMDA receptor in low-frequency magnetic field-induced anxiety in mice

It had been reported that exposure to extremely low-frequency magnetic field (ELFMF) induces anxiety in human and rodents. Anxiety mediates via the activation of N-methyl-d-aspartate (NMDA) receptor, whereas activation of γ-aminobutyric acid (GABA) receptor attenuates the same. Hence, the present study was carried out to understand the contribution of NMDA and/or GABA receptors modulation in ELFMF-induced anxiety for which Swiss albino mice were exposed to ELFMF (50?Hz, 10?G) by subjecting them to Helmholtz coils. The exposure was for 8?h/day for 7, 30, 60, 90 and 120 days. Anxiety level was assessed in elevated plus maze, open field test and social interaction test, on 7th, 30th, 60th, 90th and 120th exposure day, respectively. Moreover, the role of GABA and glutamate in ELFMF-induced anxiety was assessed by treating mice with muscimol [0.25?mg/kg intraperitoneally (i.p.)], bicuculline (1.0?mg/kg i.p.), NMDA (15?mg/kg i.p.) and MK-801 (0.03?mg/kg i.p.), as a GABA_A and NMDA receptor agonist and antagonist, respectively. Glutamate receptor agonist exacerbated while inhibitor attenuated the ELFMF-induced anxiety. In addition, levels of GABA and glutamate were determined in regions of the brain viz, cortex, striatum, hippocampus and hypothalamus. Experiments demonstrated significant elevation of GABA and glutamate levels in the hippocampus and hypothalamus. However, GABA receptor modulators did not produce significant effect on ELFMF-induced anxiety and elevated levels of GABA at tested dose. Together, these findings suggest that ELFMF significantly induced anxiety behavior, and indicated the involvement of NMDA receptor in its effect.     

S-methyl-N,N-diethylthiocarbamate sulfoxide elicits neuroprotective effect against N-methyl-D-aspartate receptor-mediated neurotoxicity

Glutamatergic neurotransmission, particularly of the NMDA receptor type, has been implicated in the excitotoxic response to several external and internal stimuli. In the present investigation, we report that S-methyl-N,N-diethylthiocarbamate sulfoxide (DETC-MeSO) selectively and specifically blocks the NMDA receptor subtype of the glutamate receptors, and attenuates glutamate-induced neurotoxicity in rat-cultured primary neurons. Other major ionotropic glutamate receptor subtypes, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate, were insensitive to DETC-MeSO both in vitro and in vivo. Disulfiram, the parent compound of DETC-MeSO, also inhibits glutamate receptors partially in vivo; however, it fails to inhibit glutamate receptors in mice pretreated with N-butyl imidazole, a cytochrome P450 enzyme inhibitor, implicating the need for bioactivation of disulfiram to be an effective antagonist. We showed that glutamate-induced increase in (45)Ca2+ was attenuated in rat-cultured primary neurons following pretreatment with DETC-MeSO. The Ca2+ influx into primary neurons, studied by confocal microscopy of the fluorescent Ca2+ dye fura-2, demonstrated a complete attenuation of NMDA-induced Ca2+ influx. Similarly, DETC-MeSO attenuated NMDA-induced (45)Ca2+ uptake. Glutamate-induced (45)Ca2+ uptake and Ca2+ influx, however, were partially blocked by DETC-MeSO, and this is consistent with both in vitro and in vivo studies in which DETC-MeSO partially blocked mouse brain glutamate receptors. In addition, DETC-MeSO pretreatment effectively prevented seizures in mice induced either by NMDA, ammonium acetate, or ethanol-induced kindling seizures, all of which are believed to be mediated by NMDA receptors. These data demonstrate that DETC-MeSO produces the neuroprotective effect through antagonism of NMDA receptors in vivo.     

Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols

NR2B selective NMDA receptor antagonists with tetrahydro-3-benzazepine-1,7-diol scaffold have been designed by formal cleavage and reconstitution of the piperidine ring of the lead compound ifenprodil (1). The secondary amine 10 represents the central building block for the synthesis of more than 25 tetrahydro-3-benzazepin-1-ols. Generally 7-hydroxy derivatives display higher NR2B receptor affinities than the corresponding 7-benzyloxy compounds. A distance of four atoms (five bond lengths) between the basic amino group and the terminal aryl moiety led to highest NR2B affinity. 3-(4-Phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-1,7-diol (WMS-1410, 25) represents the most promising NR2B antagonist of this series showing a K(i)-value of 14nM. Compound 25 reveals excellent selectivity over more than 100 further relevant target proteins, antagonizes glutamate induced excitotoxicity (IC(50)=18.4nM) and is metabolically more stable than ifenprodil. Up to a dose of 100mg/kg 25 is well tolerated by mice and it shows dose dependent analgesic activity in the late neuropathic pain phase of the formalin assay.     

大豆异黄酮对围绝经期大鼠卵巢Bax mRNA表达和Ca2+-ATP酶活性的影响

目的：观察大豆异黄酮（SI）对围绝经期大鼠卵巢BaxmRNA表达和Ca^2＋-ATP酶活性的影响。方法：采用自然老化法建立围绝经期大鼠动物模型。12月龄的初老雌性Wistar大鼠,分别给予低（50mg／kg）、中（158mg／kg）、高（500mg／kg）剂量SI灌胃处理8周。采用RT—PCR检测卵巢BaxmRNA的表达;采用化学比色法检测卵巢Ca^2＋-ATP酶活性、血清丙二醛（MDA）含量和超氧化物岐化酶（SOD）活性。结果：SI处理可使初老大鼠卵巢BaxmRNA表达和血清MDA含量降低,卵巢Ca^2＋-ATP酶活性和血清SOD活性明显升高（P〈0．05或P〈0、01）。结论：大豆异黄酮下调衰老卵巢BaxmRNA表达,提高细胞Ca2^2＋-ATP酶活性,可能是改善围绝经期卵巢功能的机制之一。     

Glycine modulates N-methyl-D-aspartic acid induced learning facilitation in rats

Summary Pretraining i.p. administration of N-methyl-D-aspartic acid (NMDA) at doses of 10 and 20mg/kg dose-dependently facilitated performance in a water T-maze learning task in rats. The effect of NMDA was inhibited by the competitive NMDA receptor antagonist CGP37849 [(DL)-E(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] (CGP) at a dose of 6mg/kg, and by the NMDA receptor complex glycine site antagonist 1-hydroxy-3-amino-2-pyrrolidone (HA-966) at a dose of 10mg/kg. The NMDA site antagonist, when given alone, did not impair learning. The glycine precursor milacemide (2-N-pentylaminoacetamide HCl), at doses of 5 and 10mg/kg accelearted learning acquisition and its effect was antagonized by HA-966. The learning rate was impaired following the administration of NMDA 10mg/kg together with milacemide 5mg/kg when compared with the effect of 10mg/kg NMDA alone.The administration of 5mg/kg NMDA was associated with an elevated tissue concentration of aspartate in the hippocampus, an effect which was antagonized by 6mg/kg of CGP. NMDA at doses of 10 and 20mg/kg elevated the concentration of glycine but decreased the concentration of aspartate, glutamate and glutamine in the cortex and aspartate in the hippocampus. The cortical effects of NMDA 10mg/kg were antagonized by 6mg/kg of CGP. Milacemide at the dose of 10mg/kg elevated glycine, aspartate, glutamate and taurine concentrations. The coadministration of 5 mg/kg NMDA with 5mg/kg milacemide elevated the concentrations of glycine, glutamate and glutamine in the cortex and taurine in the hippocampus. These amino acid levels were higher than after administration of 5mg/kg either agent alone. The results demonstrate a dose-dependent facilitation effect on learning performance by NMDA and glycine receptor agonists. Antagonists at the NMDA and glycine sites counteracted the learning improvement of NMDA, and the glycine site antagonist the effect of milacemide.     

Caspase-mediated apoptosis in neuronal excitotoxicity triggered by nitric oxide.

BACKGROUND: Excitotoxicity and excess generation of nitric oxide (NO) are believed to be fundamental mechanisms in many acute and chronic neurodegenerative disorders. Disturbance of Ca2+ homeostasis and protein nitration/nitrosylation are key features in such conditions. Recently, a family of proteases collectively known as caspases has been implicated as common executor of a variety of death signals. In addition, overactivation of poly-(ADP-ribose) polymerase (PARP) has been observed in neuronal excitotoxicity. We therefore designed this study to investigate whether triggering of caspase activity and/or activation of PARP played a role in cerebellar granule cell (CGC) apoptosis elicited by peroxynitrite (ONOO-) or NO donors. MATERIALS AND METHODS: CGC from wild-type or PARP -/- mice were exposed to various nitric oxide donors. Caspase activation and its implications for membrane alterations, Ca2+ homeostasis, intracellular proteolysis, chromatin degradation, and cell death were investigated. RESULTS: CGC exposed to NO donors undergo apoptosis, which is mediated by excess synaptic release of excitotoxic mediators. This excitotoxic mechanism differs from direct NO toxicity in some other neuronal populations and does not involve PARP activation. Inhibition of caspases with different peptide substrates prevented cell death and the related features, including intracellular proteolysis, chromatin breakdown, and translocation of phosphatidylserine to the outer surface of the cell membrane. Increased Ca2+ influx following N-methyl-D-aspartate (NMDA) receptor (NMDA-R) activation was not inhibited by caspase inhibitors. CONCLUSIONS: In CGC, NO donors elicit apoptosis by a mechanism involving excitotoxic mediators, Ca2+ overload, and subsequent activation of caspases.     

Extremely low frequency magnetic field induces hyperalgesia in mice modulated by nitric oxide synthesis

We investigated an effect of extremely low frequency magnetic field (ELF-MF, 60 Hz) on hyperalgesia using hot plate test. The level of nitric oxide (NO) and the expression of nitric oxide synthase (NOS) were measured to determine if ELF-MF is engaged in NO mediated pain mechanism. Additionally, the involvement of Ca2+-dependent NO pathway in ELF-MF induced hyperalgesia was evaluated by blocking Ca2+ sources with NMDA receptor antagonist and Ca2+ channel blocker. The exposure of mice to ELF-MF lowered pain threshold and elevated NO synthesis in brain and spinal cord. An NOS inhibitor blocked these effects of ELF-MF with attenuating the reduction of pain threshold and the rise of NO level in brain and spine by the exposure of ELF-MF. The hyperalgesic effects of ELF-MF were also blocked by a Ca2+ channel blocker, nimodipine, but not by a NMDA receptor antagonist, MK-801. The expression of Ca2+ -dependent nNOS and eNOS and Ca2+ -independent iNOS were not changed by ELF-MF. These results indicated that the exposure of ELF-MF might cause Ca2+ -dependent NOS activation, which then induces hyperalgesia with the increase in NO synthesis. In conclusion, ELF-MF may produce hyperalgesia by modulating NO synthesis via Ca2+ -dependent NOS.     

Control of postsynaptic Ca2+ influx in developing neocortex by excitatory and inhibitory neurotransmitters.

We assessed the pathways by which excitatory and inhibitory neurotransmitters elicit postsynaptic changes in [Ca2+]i in brain slices of developing rat and cat neocortex, using fura 2. Glutamate, NMDA, and quisqualate transiently elevated [Ca2%]i in all neurons. While the quisqualate response relied exclusively on voltage-gated Ca2+ channels, almost all of the NMDA-induced Ca2+ influx was via the NMDA ionophore itself, rather than through voltage-gated Ca2+ channels. Glutamate itself altered [Ca2+]i almost exclusively via the NMDA receptor. Furthermore, synaptically induced Ca2+ entry relied almost completely on NMDA receptor activation, even with low-frequency stimulation. The inhibitory neurotransmitter GABA also increased [Ca2+]i, probably via voltage-sensitive Ca2+ channels, whereas the neuromodulator acetylcholine caused Ca2+ release from intracellular stores via a muscarinic receptor. Low concentrations of these agonists produced nonperiodic [Ca2+]i oscillations, which were temporally correlated in neighbouring cells. Optical recording with Ca2(+)-sensitive indicators may thus permit the visualization of functional networks in developing cortical circuits.     

The protective effect of Ginkgo biloba extract on CCl4-induced hepatic damage

The aim of this study was to evaluate the protective effect of Ginkgo biloba extract on CCl4-induced hepatic damage in rats. Hepatic malondialdehyde, glutathione and hydroxyproline levels and histopathologic alterations in liver specimens were assessed. 200 mg/kg/day Ginkgo biloba extract were given orally to the animals for 10 days, then a single dose of 2 ml/kg b.w. carbon tetrachloride was, administered intraperitoneally. Ginkgo biloba extract treatment reduced hepatic malondialdehyde levels significantly (p < 0.05), but did not alter glutathione (p > 0.05) and hydroxyproline levels (p > 0.05). The light and electron microscopic findings showed that Ginkgo biloba extract limited the CCl4-induced hepatocyte necrosis and atrophy. These results suggest that this extract may protect the hepatocytes from carbon tetrachloride-induced liver injury.     

地西泮和戊巴比妥钠对两种小鼠镇静催眠作用强度的观察

目的：观察地西泮和戊巴比妥纳对不同种属小鼠自主活动和睡眠效应的影响,为筛选影响中枢神经系统功能的药物提供可参考的选择动物的依据。方法：分别取昆明种和ICR小鼠各40只,设对照组和地西泮给药组,每组20只,给药组ig地西泮4mg／kg,对照组给生理盐水,连续3天,末次给药后45分钟测定小鼠自主活动。另取两种小鼠各20只,分别ip戊巴比妥钠50mg／kg,观察两种小鼠的睡眠情况,记录潜伏期和睡眠时间。结果：ICR小鼠ig地西泮后,表现明显的镇静作用,自主活动的次数和对照组比较明显减少,P〈0．01;而昆明种小鼠给相同剂量的地西泮,小鼠自主活动的次数减少不明显,P〉0．05。昆明种和ICR小鼠同样ip阈上剂量的戊巴比妥钠,两者在睡眠潜伏期上无明显差异,但在睡眠时间上,则ICR小鼠的睡眠时间明显长于昆明种小鼠,P〈0．01。结论：ICR小鼠对中枢抑制药的反应性更好,适合于这类药物的筛选,尤其对作用相对较弱的中药制剂,可能提高筛选的阳性率。