复方三维右旋泛酸钙糖浆对功能性消化不良大鼠的改善作用及机制研究

目的 研究复方三维右旋泛酸钙糖浆（简称：复方糖浆）对功能性消化不良（FD）大鼠的改善作用机制。方法 48只雄性SD大鼠随机分为6组：正常组,功能性消化不良模型组,复方糖浆高、中、低剂量组(2.7、5.4、10.8 g·kg^-1)及多潘立酮组(4 mg·kg^-1)。除正常组外,其余各组均采用夹尾刺激+不规则喂养+冰生理盐水灌胃复合因素造模。各组灌胃给药14 d后,称量大鼠体重并测定胃排空率和小肠推进率,ELISA法测定血清中胃泌素（GAS）、血管活性肽（VIP）水平;Western Blot法分别检测胃窦组织干细胞生长因子（SCF）、Cx43、c-kit及结肠组织AQP4、AQP8的蛋白表达水平。结果 复方糖浆明显增加功能性消化不良大鼠体重、胃排空率及小肠推进率,提高血清胃泌素水平,降低血管活性肽水平,复方糖浆显著上调胃窦组织中干细胞生长因子、Cx43、c-kit蛋白表达及结肠组织中AQP4、AQP8蛋白表达。结论 复方糖浆可通过上调胃窦组织中干细胞生长因子、Cx43、c-kit蛋白表达而调节胃肠运动功能,并通过上调结肠组织中AQP4、AQP8蛋白表达而改善腹泻症状,进而发挥其改善功能性消化不良作用。     

HPLC法同时测定复方三维右旋泛酸钙糖浆中4中维生素的含量

目的 建立高效液相色谱(HPLC)法同时测定复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆和烟酰胺的含量。方法 采用外标法进行测定,色谱柱为Thermo Betasil C₁₈ Analytical(4.6 mm×250 mm, 5 μm),流动相为乙腈-5 mmol·L^-1十二烷基硫酸钠（含0.05%甲酸）水溶液梯度洗脱,流速1.0 mL·min^-1,检测波长260 nm,柱温30 ℃。分别测定10批复方三维右旋泛酸钙糖浆。结果 维生素B₁、维生素B₂、维生素B₆、烟酰胺4种成分的线性范围分别为5.76~115.2 μg·mL^-1(r=0.999 9)、1.16~23.20 μg·mL^-1(r=0.999 9)、1.72~34.4 μg·mL^-1(r=0.999 6)和5.76~115.2 μg·mL^-1(r=0.999 9),平均加样回收率为96.2%~98.4%(RSD为2.14%~3.42%)。不同批次复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆、烟酰胺含量范围分别为0.133 7~0.155 9、0.027 86~0.030 71、0.039 05~0.047 7、0.138 7~0.148 2 mg·g^-1。结论 该方法为完善复方三维右旋泛酸钙糖浆的质量标准和加强质量控制提供了新的方法和依据。     

复方敏维糖浆的急性毒性和长期毒性研究

摘 要 目的：为复方敏维糖浆的临床安全使用提供实验依据。方法: 急性毒性实验以小鼠为实验对象,以改良寇氏法计算半数致死量(LD₅₀)。长期毒性实验中给予大鼠高、中、低剂量（650,195 ,65 mg·kg^-1）的复方敏维糖浆,连续给药4周,停药2周后观察其一般状况、体质量、摄食量,测定血液学、血液生化学指标,解剖后裸眼观察主要靶器官( 心、肺、肾、肝) 变化。结果: 急性毒性实验中复方敏维糖浆小鼠的LD₅₀为5 581.8 mg·kg^-1。长期毒性实验中高剂量组大鼠血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆固醇（CHOL）均有一定程度升高,且大鼠自发活动减少、有困倦现象,摄食量和体质量均有一定下降。 结论:复方敏维糖浆小鼠的LD₅₀为5 581.8 mg·kg^-1,急性毒性反应与神经系统有关,未见脏器有明显损伤。长期使用高剂量复方敏维糖浆(650 mg·kg^-1) 可引起大鼠AST、ALT、CHOL升高。     

乌药对小鼠免疫功能及大鼠实验性脂肪肝的影响

目的 探讨乌药对小鼠免疫功能及大鼠实验性脂肪肝的影响。方法 乌药提取液以生药4,2,1 g·kg^-1连续灌胃给予小鼠30 d,测定给药后小鼠的脾脏指数、胸腺指数、对Con A诱导的淋巴细胞增殖能力及抗体生成细胞数;以生药2,1,0.5 g·kg^-1灌胃给予高脂饲料致实验性脂肪肝的SD大鼠,连续给药21 d后测定大鼠血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、谷丙转氨酶(ALT)和谷草转氨酶(AST)含量。结果 与对照组比较,乌药4和2 g·kg^-1均能显著提高胸腺指数和Con A诱导的淋巴细胞增殖能力及抗体生成细胞数;4和1 g·kg^-1能显著增加脾脏指数;与模型组比较,乌药2 g·kg^-1能显著降低大鼠血清TC、LDL-C、ALT、AST水平,1 g·kg^-1能显著降低血清TC、AST水平。结论 乌药能提高小鼠免疫功能,对大鼠因喂饲高脂饲料致实验性脂肪肝有一定的降脂和护肝作用。     

龙蔓藤茶辅助降血脂功能实验研究

摘 要 目的： 研究龙蔓藤茶调节血脂的作用。方法: 用高脂饲料喂养雄性SD大鼠,随机分为模型组、龙蔓藤茶高剂量组37.80 g·kg^-1、中剂量组12.60 g·kg^-1、低剂量组6.30 g·kg^-1及降脂药物组（180 mg·kg^-1）,连续给药30 d,观察各组大鼠体质量、血清总胆固醇( TC )、三酰甘油(TG)、高密度脂蛋白(HDL-C) 等指标的变化。结果:各给药组体质量增长与模型组比较,差异无统计学意义（P＞0.05）,大鼠未出现明显中毒症状;模型组实验后的TC和TG明显高于实验前（P＜0.05）;给药30 d后,与模型组比较,龙蔓藤茶37.80 g·kg^-1剂量组可显著降低高脂饲料大鼠血清TC和TG水平（P<0.05）。结论: 龙蔓藤茶具有辅助降血脂的作用。     

UHILIC-MS/MS法同时测定复方三维右旋泛酸钙糖浆中5种维生素的含量

目的 建立一种超高效亲水作用色谱串联三重四极杆质谱法（UHILIC-MS/MS）,同时测定复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆、烟酰胺和泛酸钙的含量。方法 采用超高效液相色谱仪,Waters ACQUITY BEHHILIC Amide色谱柱（2.1 mm×100 mm,1.7 μm）,以90%乙腈（含0.5%甲酸）-10 mmol/L甲酸铵水（含0.5%甲酸）为流动相,进行梯度洗脱,流速0.30 ml/min;在电喷雾（ESI）正离子模式下,用多反应监测（MRM）模式进行含量测定。结果 在5 min内,样品中5种维生素分别在各自考察的浓度范围内呈良好的线性关系,相关系数（r）均大于0.998 4;整体加样回收率在93.27%~100.39%之间,RSD为1.41%~4.96%;10批样品中维生素B₁、维生素B₂、维生素B₆、烟酰胺、泛酸钙的含量测定结果分别为32.40~38.91、7.002~8.462、9.677~11.17、33.64~39.58、3.276~3.771 mg/250 g。结论 本研究建立的UHILIC-MS/MS方法可快速实现对复方三维右旋泛酸钙糖浆中5种维生素类成分定性鉴定或定量检测,为复方三维右旋泛酸钙糖浆的开发利用和质量评价提供了可靠的技术检测方法。     

五磨饮对脾虚气滞证功能性消化不良大鼠脑肠肽的影响

目的 研究五磨饮对脾虚气滞证功能性消化不良（functional dyspepsia，FD）大鼠脑肠肽的影响，探讨其作用机制。方法 除正常组外，其余大鼠采用"慢性束缚+游泳+饮食不节"复合因素法制备脾虚气滞证FD模型。按体质量随机分为模型组、多潘立酮组、柴芍六君子汤组、五磨饮高剂量组（6.2 g·kg^-1）、中剂量组（3.1 g·kg^-1）、低剂量组（1.55 g·kg^-1）。分组后，除正常组及模型组外，其余大鼠灌胃给药干预14 d。ELISA法检测血浆胃促生长素（Ghrelin）、胃动素（motilin，MTL）、胃泌素（gastrin，GAS）、胆囊收缩素（cholecystokinin，CCK）、血管活性肠肽（vasoactive intestinal peptide，VIP）、降钙素基因相关肽（calcitonin gene related peptide，CGRP）含量，免疫组化法检测胃窦及下丘脑组织Ghrelin、MTL、GAS、CCK、VIP、CGRP表达。结果 与模型组比较，五磨饮各剂量组大鼠血浆Ghrelin、MTL含量显著增加（P<0.01或P<0.05），CCK含量显著降低（P<0.01），高剂量组和中剂量组大鼠血浆VIP含量明显降低（P<0.05），高剂量组大鼠血浆CGRP含量明显降低（P<0.05）；各剂量组大鼠胃窦组织Ghrelin、MTL、GAS、CCK、VIP、CGRP的表达差异没有统计学意义；高剂量组大鼠下丘脑组织Ghrelin表达显著增加（P<0.01），中剂量组大鼠下丘脑组织Ghrelin、MTL、GAS、VIP、CGRP表达显著增加（P<0.01）。结论 五磨饮具有调节脾虚气滞证FD大鼠脑肠肽表达的作用，这可能是其作用机制之一。     

芪防鼻敏颗粒对变应性鼻炎大鼠行为学与组织病理学的影响

摘 要 目的：探讨芪防鼻敏颗粒对变应性鼻炎（AR）大鼠行为学、鼻腔分泌物嗜酸性粒细胞（EOS）及鼻黏膜组织病理学的影响。方法: SD大鼠随机分为空白对照组、模型组、氯雷他定组（1.7 mg·kg^-1）、鼻炎康组（0.6 g·kg^-1）和芪防鼻敏颗粒高（4.6 g·kg^-1）、中（2.3g·kg^-1）,低（1.15 g·kg^-1）剂量组。采用卵清蛋白（OVA）制备AR大鼠模型,模型建立成功后,灌胃给药,每日1次,连续14 d。对各组大鼠行为学症状进行评分,检测鼻腔分泌物EOS含量,观察鼻黏膜组织病理学变化。结果: 与模型组相比,芪防鼻敏颗粒各剂量组行为学评分明显降低（P<0.01）,鼻腔分泌物EOS浸润明显下降（P<0.05或P<0.01）。组织病理学结果显示,芪防鼻敏颗粒各剂量组黏膜上皮基本完好,部分可见腺体增生,血管轻度充血,少量EOS浸润,与模型组比较,病理评分显著降低（P<0.05或P<0.01）。结论:芪防鼻敏颗粒可降低AR大鼠行为学评分,减轻鼻腔分泌物EOS浸润,改善大鼠鼻黏膜组织病理学,对AR大鼠起到一定的治疗作用。     

活犀角与犀角镇痛作用比较研究

摘 要 目的：比较活犀角与犀角对小鼠和大鼠的镇痛作用,探讨活犀角是否可以作为犀角的代用品。方法: 采用小鼠扭体法和甲醛法、大鼠热板法和热刺痛仪比较活犀角与犀角的镇痛作用。结果: 与对照组比较,活犀角3个剂量组（0.35,0.7,1.4 g·kg^-1）均能明显延长醋酸引起小鼠扭体的潜伏期（P＜0.05或P<0.01）,明显减少扭体次数（P＜0.05或P<0.01）,犀角3个剂量组（0.35,0.7,1.4 g·kg^-1）能明显减少扭体次数（P＜0.05或P<0.01）;与对照组比较,在第2次给药后,活犀角高剂量组（1.4 g·kg^-1）和犀角高,中剂量组（0.7 ,1.4 g·kg^-1）大鼠的痛阈有较明显的延长（P＜0.05或P<0.01）;与对照组比较,活犀角和犀角3个剂量组（0.175,0.35,0.7 g·kg^-1）均能显著减少甲醛引起的小鼠第二时相的镇痛作用（P<0.01）;活犀角的3个剂量组（110,220,440 mg·kg^-1）和犀角高剂量组（440 mg·kg^-1）给药前后的痛阈变化值与对照组比较明显增加（P＜0.05或P<0.01）。结论:活犀角在镇痛方面可以作为犀角的代用品使用。     

注射用益气复脉（冻干）对心力衰竭感染性休克大鼠的药效研究

目的 探讨注射用益气复脉（冻干）（YQFM）对心力衰竭感染性休克大鼠的药效作用。方法 通过结扎冠状动脉左前降支以及尾静脉推注脂多糖（LPS，25 mg·kg^-1）的方法建立心力衰竭感染性休克大鼠模型，随机将造模后大鼠分为模型组，肾上腺素（10 μg·kg^-1）组，YQFM低、高剂量（232.2、464.3 mg·kg^-1）组，联合给药（肾上腺素10 μg·kg^-1＋YQFM 464.3 mg·kg^-1）组，假手术组进行同样操作但不结扎不推注LPS。造模后即给药，尾iv给药1次，模型组和假手术组大鼠给予等体积的0.9%氯化钠注射液。使用八通道无创血压仪检测造模前、造模后及给药后大鼠收缩压变化；ELISA法检测各组大鼠血清中脑钠肽（BNP）、氨基端前心钠肽（NT-proANP）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和超氧化物歧化酶（SOD）水平。结果 各组大鼠的基础收缩压无显著性差异，与假手术组比较，造模各组大鼠收缩压显著降低（P＜0.001）；与模型组比较，各给药组大鼠收缩压显著回升（P＜0.05、0.001）。与假手术组相比，模型组血清NT-proANP、BNP、CK-MB、LDH、ALT、AST水平显著升高（P＜0.001），SOD水平显著降低（P＜0.001）；与模型组相比，肾上腺素组，YQFM 232.2、464.3 mg·kg^-1组和联合给药组的NT-proANP、BNP、CK-MB、LDH、ALT、AST水平均显著下降（P＜0.05、0.01、0.001），肾上腺素组、YQFM 464.3 mg·kg^-1组和联合给药组SOD水平显著升高（P＜0.05、0.01、0.001）。结论 YQFM可以显著回升心力衰竭感染性休克大鼠的收缩压水平，改善血清中相关生化指标水平，并且与肾上腺素联合应用效果最好。     

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.     

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.     

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.