大环内酯类抗生素麦迪霉素的电化学特性

在K₂HPO₄,NH₄Cl+NH₃和NaOH的10%(v/v)乙醇水溶液中,除0.01mol·L^-1以上NaOH液作为支持电解质外,麦迪霉素的伏安波皆为两个峰。峰A相当于它的甲醛基还原波,峰B为催化吸附氢波。溶液pH对两峰有强烈的影响。实验表明伏安波有吸附特性,且不可逆。两峰的ip与麦迪霉素的浓度成正比,线性范围分别为3×10^-6～3×10^-5mol·L^-1和1×10^-7～4×10^-5mol·L^-1,检测限为:1×10-6mol·L^-1和5×10^-8mol·L^-1。可应用于麦迪霉素的定量测定。研究了两峰的特性和电极机理,测定了有关的物理常数。     

阿西美辛在高锰酸钾-亚硫酸钠体系中的流动注射化学发光分析

目的研究阿西美辛对高锰酸钾-亚硫酸钠化学发光体系的增敏作用，建立阿西美辛的简便、快速测定新方法。 方法利用阿西美辛对高锰酸钾-亚硫酸钠化学发光体系的增敏作用,结合流动注射技术对其含量进行定量测定。 结果在1.0×10^-2 mol·L^-1 H₃PO₄ - 5.0×10^-5 mol·L^-1 KMnO₄ - 4.0×10^-4 mol·L^-1 Na₂SO₃体系中，化学发光强度与阿西美辛浓度在1.0×10^-7-1.0×10^-5 mol·L^-1呈线性关系，在3倍信噪比，阿西美辛的检出限为6.9×10^-8 mol·L^-1，对2.5×10^-6 mol·L^-1阿西美辛测定获得满意结果。结论该方法快速、简便、准确度好、灵敏度高、选择性好,对临床医学研究具有实际意义。     

银杏内酯B对大鼠中性白细胞花生四烯酸代谢酶和细胞内钙水平的影响

目的　观察银杏内酯B对大鼠中性白细胞花生四烯酸代谢酶及细胞内钙水平的影响。方法　反相高效液相色谱及Fura-2/AM荧光指示剂法。结果　银杏内酯B在0.1-10μmol·L^-1范围内,使花生四烯酸释放量降低10.9%-22.2%;0.1-50μmol·L^-1时,LTB₄和5-HETE生成量分别降低29.4%-88.6%和26.2%-89.3%;在0.1-100μmol·L^-1使PAF和fMLP刺激引起的细胞内游离钙浓度分别降低13.9%-51.4%和2.2%-36.6%。结论　银杏内酯B能抑制体外大鼠中性白细胞花生四烯酸代谢酶的活性及细胞内游离钙浓度的升高。     

鱼藤素降低小鼠神经母细胞瘤细胞Neuro-2A存活率的实验研究

摘 要 目的： 研究鱼藤素对小鼠神经母细胞瘤细胞Neuro-2A (N2A)存活率及凋亡的影响。方法: N2A细胞以5×10⁴·ml^-1密度接种到细胞培养板中,1×10^-8 mol·L^-1鱼藤素处理后6,12,24,48,72 h等5个时间点上测定细胞存活率;加入鱼藤素0,1×10^-11,1×10^-10,1×10^-9,1×10^-8,1×10^-7,1×10^-6 mol·L^-1等7个不同浓度干预48 h后测定细胞存活率。2×10^-8 mol·L^-1鱼藤素干预24 h,测定细胞匀浆中caspase 3活力。结果:5×10⁴·ml^-1 N2A细胞以含10%胎牛血清DMEM培养基培养,第48 h达到细胞生长曲线的峰值。1×10^-8 mol·L^-1鱼藤素干预24～72 h,时间依赖性显著降低N2A细胞存活率(P<0.05);在鱼藤素干预48 h时间点上,1×10^-8～1×10^-6·mol·L^-1浓度范围内剂量依赖性可显著降低N2A细胞存活率(P<0.05),其IC₅₀=1.6×10^-8 mol·L^-1。鱼藤素作用于N2A细胞24 h可显著提高caspase 3活力,约达到对照组的5.6倍。结论: 鱼藤素可时间依赖性且剂量依赖性降低N2A细胞存活率,可能与增加caspase 3活力有关。     

西红花苷对牛主动脉平滑肌细胞内钙离子浓度的影响

目的研究西红花苷对血管平滑肌细胞内钙离子浓度的影响。方法以Fluo-3/AM作为Ca²⁺荧光探针,采用激光扫描共聚焦显微镜观察牛主动脉平滑肌细胞内钙离子浓度的变化。结果无论细胞外有无钙离子,西红花苷(1×10^-8,1×10^-7,1×10^-6 mol·L^-1)均能明显抑制1×10^-2 mol·L^-1 H₂O₂引起的细胞内钙离子浓度的升高,其抑制率含钙条件下分别为34.1%, 57.1%和74.3%(P<0.01),无钙条件下分别为26.2%,32.1%和50.0%(P<0.01);在胞外无钙的条件下,西红花苷 (1×10^-8,1×10^-7,1×10^-6 mol·L^-1)能抑制70 mmol·L^-1 CHCl₃导致雷洛丁敏感钙池的释放,其抑制率分别为27.8%, 27.8%和50.0% (P<0.01)。结论西红花苷能抑制胞外钙离子的内流及内质网上钙离子的释放。     

马蔺子素的单扫描示波极谱法测定

目的建立测定马蔺子素的极谱法。方法单扫描示波极谱法。结果在8.0×10^-3 mol·L^-1 Na₂B₄O₇-1.6×10^-2 mol·L^-1 KH₂PO₄ (pH 7.7)支持电解质中,马蔺子素有一灵敏的极谱还原波,其峰电位E_p=-1.23 V(vs SCE),二阶导数峰电流i_p″与马蔺子素浓度为1.5×10^-7～5.2×10^-6 mol·L^-1呈良好线性关系(γ=0.9992,N=9),检出限为6.0×10^-8 mol·L^-1。13次测量2.0×10^-6 mol·L^-1马蔺子素还原波二阶导数峰峰电流,相对标准偏差RSD为0.87%。结论该方法灵敏、简便、快速,可用于原料药及胶囊中马蔺子素含量的测定。     

组胺H2受体激动剂和拮抗剂及抗癌药对正常人造血祖细胞和HL-60白血病细胞生长的作用

采用体外微量克隆培养体系研究了组胺H2受体激动剂4-甲基组胺(4-MH)和拮抗剂雷尼替叮(ranitidine)及抗癌药阿糖胞苷分别对正常人外周血粒-巨噬系祖细胞(PBCFU-GM)和HL-60白血病细胞生长的作用。当4-MH的浓度为10^-9～10^-6mol·L^-1时,可促进PBCFU-GM的增殖,4-MH的浓度增加至10^-4mol·L^-1时则表现为抑制PBCFU-GM的增殖。Ranitidine的浓度为10^-9～10^-5mol·L^-1时,表现出对PBCFU-GM增殖的抑制作用,但在10-6mol·L^-1剂量时对PBCFU-GM的抑制率低于50%,而在该剂量时对HL-60白血病细胞的抑制率已达100%,具有一定的选择性。抗癌药阿糖胞苷(Ara-C)对HL-60白血病细胞的抑制作用比对PBCFU-GM的抑制作用较强,但两者的IC₅₀值处于同一个数量级。在强化化疗剂量10^-5mol·L^-1时,Ara-C对HL-60白血病细胞和PBCFU-GM正常造血祖细胞的抑制率均达100%。     

大黄素的极谱行为及应用研究

在H₃BO₃-Na₂B₄O₇(pH8.5)底液中,大黄素在单扫示波极谱仪上于-0.75V(vs.SCE)左右有一灵敏的二阶导数峰,峰电流与浓度在1.42×10^-7～5.7×10^-6mol·L^-1和7.1×10^-6～7.1×10^-5mol·L^-1范围内呈良好的线性关系,检测限为0.7×10^-7mol·L^-1。本法操作简便、快速、灵敏、选择性好,应用于中药大黄中大黄素的测定,结果良好。本文还研究了大黄素的极谱行为及电极反应机理,并用电化学方法讨论了大黄素、大黄酸、大黄酚、大黄素甲醚和芦荟大黄素清除由邻苯三酚自氧化产生的超氧自由基(O^·-₂)的作用。     

碳糊电极阳极伏安法测定秋水仙碱

在0.05mol·L^-1H₂SO₄介质中,用碳糊电极(石墨粉:液体石蜡油=1.5∶1)阳极扫描伏安法测定秋水仙碱,检测限1×10^-7mol·L^-1,检测线性范围4.0×10^-7～1×10^-3mol·L^-1,氧化时出现两个氧化峰,峰电位分别为1.07V和1.33VvsSCE,峰电位随pH值升高而正移。对原料和片剂进行了测定,均获得满意的结果。     

浮石修饰碳糊电极差示脉冲吸附伏安法测定盐酸普鲁卡因

目的:建立一种新型化学修饰电极吸附伏安法测定盐酸普鲁卡因的分析方法。方法:在1-25 ×10^-3mol·L^-1 KH₂PO₄ 和1-25×10^-3mol·L^-1 Na2HPO4 混合缓冲溶液(pH6-88,25 ℃) 中,用6% 浮石修饰碳糊电极,差示脉冲吸附伏安法测定盐酸普鲁卡因。结果:盐酸普鲁卡因的阳极峰电位为+ 0-98 V(vs.SCE),峰电流与盐酸普鲁卡因浓度在9-1×10- 7 ～2-6 ×10-5mol·L^-1 范围内呈良好的线性关系,检测下限为5-0 ×10^-8mol·L^-1 ,回收率为95-2%～104-8% ,RSD为3-2% 。结论:本法快速、简便、准确、灵敏度高,直接用于盐酸普鲁卡因注射液的测定,得到满意的结果。     

依布硒啉衍生物对白三烯B4生物合成抑制作用及其构效关系

目的：研究一系列依布硒啉衍生物对白三烯B₄生物合成的影响,并探讨其构效关系。方法：高效液相色谱法测定白三烯B₄。结果：依布硒啉的磺酰胺类似物以及N-芳香环取代的磺酰胺衍生物对白三烯B4生物合成具有抑制作用,其IC₅₀在10^-5～10^-6 mol.L^-1之间,并存在一定的构效关系。结论：磺酰胺基团上的酸性氢原子是关键因素,它的存在可以形成分子内氢键,从而使化合物具有活性。     

白三烯B4放射受体结合测定方法的建立及其特性的分析

白三烯Ｂ＿４放射受体结合测定方法的建立及其特性的分析赵宁，朱秀媛，程桂芳（中国医学科学院，中国协和医科大学药物研究所，北京１０００５０）白三烯Ｂ４（ｌｅｕｋｏｔｒｉｅｎｅＢ４，ＬＴＢ４）是花生四烯酸（ａｒａｃｈｉｄｏｎｉｃａｃｉｄ）５－脂氧酶代谢产物...     

Effect of Nedocromil Sodium on Sulfidopeptide Leukotrienes-stimulated Human Alveolar Macrophages in Asthma

Summary: Alveolar macrophages (AM) may take part in the amplification of the inflammatory mechanism involved in asthma. During an asthma attack, mast cells and eosinophils release arachidonic acid derivative mediators of inflammation such as sulfidopeptide leukotrienes. Among them, LTC₄ has been shown to be present in bronchoalveolar fluid. In asthmatic patients, we showed that the ability of AM to transform LTC₄ into its derivatives LTD₄ and LTE₄ was related to the intensity of the local inflammation observed during endoscopy. AM from asthmatics incubated in the presence of LTC₄ or LTE₄, generated LTB₄ and 5-HETE, which are potent chemoattractants. Nedocromil sodium (10^-4 M) decreased LTB₄ releasability and intracellular 5-HETE concentrations in zymosan-stimulated AM from asthmatic patients, and was shown to decrease the LTC₄ or LTE₄-promoted formation of LTB₄ and 5-HETE.     

山莨菪碱对大鼠胸水中性白细胞花生四烯酸代谢的影响

本文研究了654-2对大鼠胸水中性白细胞代谢[1-¹⁴C]AA及内源性AA的影响。大鼠白细胞AA经5-LPO代谢途径形成的主要产物为LTB₄及5-HETE,经CO途径的主要产物为HHT及TXB₂。654-2对白细胞代谢[1-¹⁴C]AA无抑制作用,但显著减少白细胞从内源性AA形成的LTB₄,5-HETE,HHT及TXB₂。这种抑制作用与654-2呈剂量依赖关系。本实验结果表明,654-2抑制PG及LT的形成可能是影响了AA从胞膜的释放,而并非直接抑制CO及5-LPO。     

Inhibition of Leukotriene Biosynthesis and Polymorphonuclear Leukocyte Functions by Orally Active Quinolylmethoxyphenylamines

Abstract: The N-substituted quinolylmethoxyphenylamines, ETH603, ETH615 and ETH647, inhibited the formation of LTB₄ in rat peritoneal leukocytes, human peripheral polymorphonuclear leukocytes and canine whole blood. In rat and human cells, the compounds also inhibited the formation of 5-HETE and stimulated the synthesis of 15-HETE. In rat leukocytes, the compounds were 15–30 times more potent inhibitors of LTB₄ synthesis than nordihydroguaiaretic acid, but in canine whole blood they were significantly less potent, possibly due to protein binding. However, after oral administration of the compounds to dogs a long-lasting inhibition of LTB₄ production in peripheral blood was observed at serum concentrations much lower than those required in vitro. Furthermore, the compounds inhibited the LTB₄-directed chemotaxis and the phagocytosis of C. albicans blastospores by canine polymorphonuclear leukocytes both in vitro and following oral administration. The calcium ionophore A23187-induced release of LTB₄ in the peritoneal cavity of rats was also inhibited by systemic administration of the compounds. We therefore conclude that these novel quinolines are orally active 5-lipoxygenase inhibitors which may accumulate in inflammatory cells in vivo, leading to potent inhibition of leukotriene biosynthesis and cell function.     

Anti-inflammatory activities of Emblica officinalis Gaertn leaf extracts

Abstract— Emblica officinalis Gaertn, a tree growing in subtropical and tropical parts of China, India, Indonesia and the Malay Peninsula, has been used for anti-inflammatory and antipyretic treatments of rural populations in these areas. In the present study, we examined the effects of Emblica officinalis extracts on carrageenan- and dextran-induced rat hind paw oedema. Anti-inflammatory activity was found in the water fraction of methanol extract of the plant leaves. The effects of the same fraction were tested on the synthesis of mediators of inflammation such as leukotriene B₄ (LTB₄), platelet-activating factor (PAF) and thromboxane B₂ (TXB₂), and on LTB₄- and N-formyl-l -methionyl-l -leucyl-l -phenylalanine (FMLP)-induced migration of human polymorphonuclear leucocytes (PMNs) in-vitro. The water fraction of the methanol extract inhibited migration of human PMNs in relatively low concentrations. It did not inhibit LTB4 or PAF synthesis in human PMNs or TXB₂ synthesis in human platelets during clotting, suggesting that the mechanism of the anti-inflammatory action found in the rat paw model does not involve inhibition of the synthesis of the measured lipid mediators.     

The development of methodology for clinical measurement of 5-lipoxygenase pathway intermediates from human peripheral blood mononuclear cells

Recent studies have shown a correlation between 5-lipoxygenase (5-LO) pathway up-regulation and cardiovascular risk. Despite the existence of several assays for products of the 5-LO pathway, a reliable method for clinical determination of 5-LO activity remains to be established. In the present communication, we report conditions that allow measurement of 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B₄ (LTB₄) in peripheral blood mononuclear cells (PBMCs) isolated from the blood of atherosclerosis patients before and after stimulation by the calcium ionophore, A23187. LTB₄, a potent mediator of inflammation-linked cardiovascular disease, was measured using an existing competitive enzyme immunoassay (EIA) kit after making specific methodological improvements that allowed PBMCs to be used in this format for the first time. LTB₄ was also measured by LC/MS/MS along with 5-HETE, a direct by-product of the action of 5-LO on arachidonic acid and a molecule for which no commercial EIA kit exists. The LC/MS/MS assay was validated over a range of 0.025–25 ng/mL for LTB₄ and 0.1–25 ng/mL for 5-HETE. The EIA method has a validated range covering 0.025–4 ng/mL. When both assays were applied to analyze LTB₄ from stimulated PBMCs isolated from 25 subjects with various degrees of atherosclerosis, a high correlation was obtained (r = 0.9426, Pearson's correlation coefficient). A high correlation was also observed between the levels of LTB₄ and 5-HETE measured by LC/MS/MS after ionophore stimulation (r = 0.9159). Details are presented for optimized sample collection, processing, storage, and analysis in accordance with the logistical demands of clinical analysis.     

白细胞介素类及白三烯类等炎性介质对肿瘤坏死因子α产生的影响

目的：研究白细胞介素类及白三烯类等炎性介质对小鼠腹腔巨噬细胞生成及分泌肿瘤坏死因子α(TNFα)的影响。方法：用L929作为靶细胞的结晶紫染色法测定巨噬细胞培养上清液及胞溶部分TNFα的含量。结果：重组鼠白细胞介素-1β(rmIL-1β)和重组人白细胞介素-8(rhIL-8)均能促进巨噬细胞产生TNFα,其中rhIL-8有很好的剂量相关性,对巨噬细胞胞溶部分的TNFα无影响;重组人白细胞介素-6(rhIL-6),白三烯B₄(LTB₄),白三烯C₄(LTC₄)及白三烯D₄(LTD₄)均不能促进巨噬细胞生成及分泌TNFα。结论：rhIL-8和rmIL-1β能促进小鼠腹腔巨噬细胞生成TNFα。rhIL-6, LTB₄, LTC₄和LTD₄对TNFα生成无影响。     

Inhibition of LTB4 biosynthesis in situ by CGS 23885, a potent 5-lipoxygenase inhibitor, correlates with its pleural fluid concentrations in an experimentally induced rat pleurisy model

An intrapleural injection of carrageenan in rats induced LTB₄ and LTC₄/D₄/E₄ biosynthesis, exudate formation, and cellular influx in the pleural cavity. An injection of calcium ionophore (A23187, 100nmol) 16–18h after carrageenan injection augmented leukotriene biosynthesis and exudate formation, but not cellular influx. The carrageenan-induced pleurisy model modifid by A23187 administration was used to study the oral effect of CGS 23885 (N-hydroxy-N-[(6-phenoxy-2H-1-benzopyran-3-yl)-methyl]urea), a potent 5-lipoxygenase (5-LO) inhibitor, on inflammatory parameters. CGS 23885 dose-dependently (1 to 30mg/kg) inhibited the enhanced LTB₄ and LTC₄/D₄/E₄ (1 to 10mg/kg) biosynthesis, but had no effect on enhanced exudate formation. An inhibitory effect of CGS 23885 of small magnitude on cellular influx due to carrageenan stimulation was seen at 30mg/kg. The concentrations of CGS 23885 in the pleural fluid were dose-related, and a positive correlation (r ²=0.989) between pleural fluid concentration of LTB₄ and CGS 23885 was observed. The results confirm that CGS 23885 is a specific, orally active 5-LO inhibitor which can achieve concentrations in the pleural cavity sufficient to inhibit production of LTB₄ and LTC₄/D₄/E₄ in an ongoing inflammatory response. Received: 9 February 1995 / Accepted: 20 December 1996     

红海榄叶的化学组成及其生物活性

红树植物是一类生长在热带和亚热带沿海潮间带并受周期性洁水浸淹的木本植物[1].