文冠果壳提取物对β-淀粉样蛋白致动物学习记忆障碍的改善作用

目的研究文冠果壳乙醇提取物对动物学习记忆障碍的改善作用并探讨其可能的作用机制。方法采用水迷宫法、避暗法测定小鼠的学习记忆能力;用Y迷宫法及Morris水迷宫法测试大鼠的学习记忆能力,显微镜下观察海马组织形态学改变。结果文冠果壳乙醇提取物显著减少侧脑室注射β-淀粉样蛋白(25-35)(Aβ(25-35))致记忆障碍小鼠水迷宫实验的逃避潜伏期和避暗实验的错误次数,延长避暗潜伏期;文冠果壳乙醇提取物显著提高D-半乳糖合用Aβ(25-35)致记忆障碍大鼠Y迷宫测试中正确反应率,显著缩短Morris水迷宫测试中的潜伏期及游泳路程;抑制海马神经元的变性及脱落。结论文冠果壳乙醇提取物对Aβ(25-35)致鼠学习记忆障碍有显著的改善作用,其作用机制可能与对抗Aβ(25-35)的毒性有关。     

羟基查尔酮类衍生物C8对东莨菪碱致痴呆小鼠学习记忆的影响

目的：观察羟基查尔酮类衍生物C8对东莨菪碱诱导的记忆障碍小鼠学习记忆的影响。方法：实验小鼠除空白对照组、东莨菪碱组（模型组）灌服0.5%CMC-Na溶液外,C8给药组（高、低2个剂量组）灌服C8,阳性对照组灌服吡拉西坦,连续灌胃22d。从第15天起进行Morris水迷宫试验,连续8d。结果：C8能明显缩短定位航行实验中模型小鼠的逃避潜伏期,明显延长空间探索实验中模型小鼠在原平台所在象限的游泳时间。结论：C8对东莨菪碱引起的小鼠学习记忆能力障碍有改善作用。     

中药海龙抗D-半乳糖诱导衰老小鼠学习记忆损伤作用研究

目的 研究中药海龙对D-半乳糖诱导衰老小鼠学习记忆损伤的影响及其作用机制。方法 采用高效液相色谱（HPLC）技术测定海龙中抗学习记忆损伤有效成分二十二碳六烯酸（DHA）含量;腹腔注射D-半乳糖(D-gal)制备衰老小鼠模型,以Morris水迷宫实验及蛋白免疫印迹法等,对小鼠学习记忆能力、海马组织氧化损伤相关生化指标及蛋白表达进行检测,探究海龙对衰老小鼠学习记忆损伤的保护作用及其机制。结果 HPLC结果显示,海龙中DHA含量为7.761 3 mg/g（以生药计）,约占总成分的47%;Morris水迷宫实验结果显示,海龙可减少学习记忆损伤小鼠逃避潜伏期时间,增加小鼠目标象限游泳时间、游泳路程占比、穿台次数,改善小鼠学习记忆损伤;此外,海龙可激活衰老小鼠海马组织AKT/FOXO1/SOD2信号通路,上调氧化应激通路相关蛋白表达,降低衰老小鼠海马组织氧化损伤程度改善小鼠学习记忆损伤。结论 本研究发现海龙富含二十二碳六烯酸,具有改善D-半乳糖诱导衰老小鼠学习记忆损伤的作用,并初步阐明其作用机制与抗氧化相关,为中药海龙抗学习记忆损伤研究提供了实验依据。     

银杏叶提取物对东莨菪碱所大鼠空间工作记忆障碍的影响

目的 探讨银杏叶提取物对东莨菪碱所致大鼠空间工作记忆障碍的影响.方法 大鼠随机分成3组:正常组、东莨菪碱组和银杏叶治疗组.水迷宫试验,东莨菪碱组按0.4mg/kg腹腔注射,以后每天注射等体积生理盐水,连用6d.正常对照组每天注射与东莨菪碱等体积的生理盐水连用6d;银杏叶治疗组按10mg/kg腹腔注射,1次/d,连用6d.1周后进行Morris水迷宫试验,观察3组大鼠平台逃避潜伏期,并与实验后第1天比较.结果 两次逃避潜伏期在正常组呈非常显著性差异(46.4±17.7,13.4±8.2,P<0.01)东莨菪碱组无统计学差异(23.6±14.3,18.1±9.8,P>0.05),银杏叶组呈显著性差异(27.9±14.3,9.0±3.8,P<0.05).结论 M-型胆碱能受体阻滞剂东莨菪碱能损害大鼠空间工作记忆,银杏叶提取物能改善这种损害,说明银杏叶提取物是通过影响胆碱能系统来发挥其促智作用的.     

1,1’-(联苯基-4,4’)-二[3-(二甲氨基)-1-丙酮]对阿尔茨海默病小鼠的影响

目的 研究1,1’-(联苯基-4,4’)-二[3-(二甲氨基)-1-丙酮](BDBDP)对东莨菪碱致小鼠阿尔茨海默病(AD)的作用及其机制.方法 将50只ICR小鼠随机分为正常组、模型组及BDBDP低、中、高剂量组.连续ip给药18d,第13天ip东莨菪碱造模,并采用Morris水迷宫及Y迷宫进行行为学测试;测定小鼠脑组织中乙酰胆碱酯酶(AChE)、胆碱乙酰转移酶(ChAT)、超氧化物歧化酶(SOD)的活性.结果 BDBDP能缩短水迷宫实验中小鼠的逃避潜伏期,并提高目标象的限滞留时间;可提高Y迷宫试验中小鼠的自发交替率,且不影响小鼠的活动能力;还能降低小鼠脑组织中AChE的活性,提高ChAT和SOD的活性.结论 BDBDP对东莨菪碱所致小鼠AD模型有明显改善作用,其机制可能与其作用于胆碱能系统及其抗氧化作用有关.     

包载橙皮素纳米脂质体对于血管性痴呆小鼠学习记忆能力改善作用的实验研究

摘要：目的:研究包载橙皮素（HES）纳米脂质体对于血管性痴呆（VD）小鼠学习记忆能力的改善作用及其机制。方法:应用薄膜分散法结合超声水化技术制备包载HES的纳米脂质体并对其进行质量表征。随机选取60只C57BL/6清洁级小鼠,应用短暂性夹闭双侧劲总动脉法建立小鼠VD模型后,随机分成假手术组、VD模型组、HES溶液组及HES纳米脂质体组,分别给予相应形式药物干预。药物治疗结束后应用Morris水迷宫评价各组小鼠的学习及记忆能力,同时HE染色观察各组小鼠海马神经元细胞排列情况;通过ELISA法及Western Blotting技术测定脑内氧化应激水平及其分子机制。结果:包载HES纳米脂质体形态圆整、分散性好,粒径均一,包封率高达（86.37±3.21）%。Morris水迷宫及HE染色结果显示,相比于假手术组,VD模型组小鼠平均逃避潜伏期显著增加（P<0.05）,平台穿越次数及停留时间显著下降（P<0.05）。相比于VD模型组,HES溶液组及HES纳米脂质体组小鼠的平均逃避潜伏期显著下降（P<0.05）,而平台穿越次数和停留时间显著增加（P<0.05）,同时HES纳米脂质体的平均逃避潜伏期、平台穿越次数及停留时间较HES溶液组有显著差异（P<0.05）。分子生物学检测结果显示,相比于模型组,HES纳米脂质体组的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-PX）及核因子E2相关因子（Nrf2）、醌氧化还原酶1（NQO1）、血红素加氧酶-1（HO-1）蛋白表达显著增加（P<0.05）,而丙二醛（MDA）含量显著下降（P<0.05）。结论:HES纳米脂质体可能通过激活Nrf2信号通路,抑制氧化应激损伤,从而改善VD小鼠的学习记忆能力;同时应用纳米脂质体包载药物还能显著增加药物的治疗效果,有望成为防治VD的新型治疗药物治疗形式。     

补肾壮阳胶囊对小鼠认知功能障碍的改善作用及机制研究

目的：本文从补肾壮阳胶囊（WSKY）改善精神分裂症模型小鼠认知功能障碍进行研究,以探究其可能的作用机制。方法：采用地卓西平马来酸盐（MK-801）建立精神分裂症模型。动物行为学方面,运用Morris水迷宫实验评价补肾壮阳胶囊对精神分裂症小鼠认知功能障碍的治疗效应;组织生物化学方面,运用实时荧光定量PCR（RT-PCR）和蛋白免疫印迹（Western blot）的方法考察补肾壮阳胶囊对脑源性神经营养因子（BDNF）、钙调蛋白激酶Ⅱ（CaMKⅡ）、环腺苷酸反应元件结合蛋白（CREB）的mRNA和细胞外信号调节激酶（ERK）蛋白表达的影响。结果：WSKY中、高剂量组小鼠Morris水迷宫定位航行逃避潜伏期小于模型组,而其空间探索穿过原平台所在位置的次数、在原平台所在象限搜索的时间百分比均大于模型组（P<0.05）;WSKY中、高剂量可以增加BDNF mRNA的含量和ERK蛋白的表达。结论：WSKY中、高剂量可以改善精神分裂症小鼠的认知功能障碍,其作用机制与WSKY提高精神分裂症小鼠海马区BDNF mRNA的表达和增加ERK蛋白含量有关。     

盐附子对小鼠的急性神经毒性作用

目的 研究盐附子(SAC)对小鼠神经系统的急性毒性作用.方法 采用小鼠自发活动、爬杆、Morris水迷宫试验,分别设SAC生药7.68、3.84、1.92 g·kg-1剂量组,ig给药,同时设阴性对照和阳性对照组.单次给药后15、60 min用自发活动仪测定小鼠在10 min内自发活动的次数;单次给药30 min后将小鼠放在爬杆架的玻璃棒上,记录小鼠爬杆时间;连续给药4 d,末次给药后30 min进行水迷宫试验,以小鼠找到隐藏平台的时间为逃避潜伏期.结果 SAC高、中、低剂量组的小鼠自发活动次数、爬杆时间、逃避潜伏期与对照组相应指标相比,差异无统计学意义(P＞0.05).结论 SAC浓度为7.68、3.84、1.92 g·kg-时,未观察到其对小鼠神经系统的急性毒性作用.     

5-羟甲基-2-呋喃甲醛衍生物的合成及降血糖活性评价

目的设计合成5-羟甲基-2-呋喃甲醛（5-HMF）衍生物,并评价其降血糖活性,寻找新型降血糖化合物。方法以5-羟甲基-2-呋喃甲醛为起始原料,分别经缩合、酯化、苄基化、脱苄基等反应合成目标化合物。通过测试目标化合物对葡萄糖促吸收率的影响评价化合物的活性。结果合成了14个未见文献报道的新化合物,其化学结构经。H—NIVlR、MS谱确证。结论生物活性评价结果显示,8个目标化合物（1～7、14）具有良好的降血糖活性,其中,化合物6的降血糖活性最好,其葡萄糖促吸收率为87．45％。     

白藜芦醇及其类似物的合成及抗TPA促癌作用研究

目的设计合成白藜芦醇类似物 ,并测试其抗佛波酯 (TPA)促癌作用。方法以 3,5 二羟基苯甲酸为原料经多步反应合成目标化合物 ,采用TPA致小鼠耳肿胀促癌法确定目标化合物抗TPA促癌作用。结果所有合成的目标化合物通过1H NMR确认其结构 ,大部分化合物具有明显的抗TPA促癌作用。结论白藜芦醇及其类似物具有较强抗TPA促癌作用。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.