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中国中医药科技 2009年第1期16卷 30-31页

作者：张莉陈乃富谷仿丽杨传彬戴军皖西学院化学与生命科学系六安237012

目的:研究蕨菜黄酮提取物对小鼠免疫功能的影响。方法:实验设正常对照组、蕨菜黄酮低剂量组、中剂量组、高剂量组。小鼠灌胃40天后,测定小鼠的脏器体重比值,观察迟发型变态反应(DTH)、单核-巨噬细胞碳廓清和血清溶血素等指标。结果:蕨... 详细信息

目的:研究蕨菜黄酮提取物对小鼠免疫功能的影响。方法:实验设正常对照组、蕨菜黄酮低剂量组、中剂量组、高剂量组。小鼠灌胃40天后,测定小鼠的脏器体重比值,观察迟发型变态反应(DTH)、单核-巨噬细胞碳廓清和血清溶血素等指标。结果:蕨菜黄酮提取物中剂量能显著提高小鼠足跖肿胀度,显著增强巨噬细胞的吞噬功能,显著提高血清溶血素抗体生成。结论:蕨菜黄酮对免疫功能有一定的增强作用。

关键词：厥菜黄酮提取物/药理学肝/药物作用脾/药物作用胸腺/药物作用抗体生成小鼠

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海帕刺桐碱药理作用的研究

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中国中医药科技 2009年第5期16卷 372-373页

作者：陈学芬钟正贤李燕婧黄平广西中医药研究院南宁530022

目的:探讨海帕刺桐碱的药理作用。方法:采用小鼠耳廓肿胀法、免疫器官重量和溶血素生成方法,四氯化碳(CCl4)和异硫氰酸萘酯制备肝损伤模型;观察海帕刺桐碱抗炎、免疫增强和抗肝损伤作用。结果:海帕刺桐碱大、小剂量组均明显减少小鼠耳... 详细信息

目的:探讨海帕刺桐碱的药理作用。方法:采用小鼠耳廓肿胀法、免疫器官重量和溶血素生成方法,四氯化碳(CCl4)和异硫氰酸萘酯制备肝损伤模型;观察海帕刺桐碱抗炎、免疫增强和抗肝损伤作用。结果:海帕刺桐碱大、小剂量组均明显减少小鼠耳廓重量;增加小鼠胸腺、脾脏重量,提高小鼠血清溶血素水平;明显降低CCl4和异硫氰酸萘酯所致肝损伤小鼠血清中转氨酶活性及胆红素含量。结论:海帕刺桐碱具有抗炎、免疫增强和抗肝损伤作用。

关键词：海帕刺桐碱/药理学胸腺/药物作用脾/药物作用抗体生成/药物作用小鼠

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蜂花粉对蛋鸡免疫器官组织结构的影响

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中国中医药科技 2007年第5期14卷 351-352页

作者：王珏金光明李升和何倩倩张贺超安徽科技学院凤阳233100

目的:探讨蜂花粉对蛋鸡免疫器官发育的影响。方法:取200羽50日龄健康罗曼褐壳蛋鸡,随机分为2组,对照组饲喂基础日粮,实验组在基础日粮中添加1.5%的蜂花粉,分别于90、150、210、380天每组随机取鸡6羽,颈静脉放血致死,解剖取胸腺、腔上囊... 详细信息

目的:探讨蜂花粉对蛋鸡免疫器官发育的影响。方法:取200羽50日龄健康罗曼褐壳蛋鸡,随机分为2组,对照组饲喂基础日粮,实验组在基础日粮中添加1.5%的蜂花粉,分别于90、150、210、380天每组随机取鸡6羽,颈静脉放血致死,解剖取胸腺、腔上囊和脾,称重并取材,制作石蜡切片,显微镜下观察。结果:90天实验组蛋鸡的胸腺和腔上囊平均质量和器官指数极显著高于对照组(P<0.01),脾脏平均质量显著高于对照组(P<0.05);150天脾脏和腔上囊平均质量和器官指数显著或极显著高于对照组(P<0.05或P<0.01);210天腔上囊的平均质量和器官指数极显著高于对照组(P<0.01);380天除脾脏器官指数差异显著外,其他差异不显著。实验组的腔上囊小结皮质增厚,退化时间延迟;胸腺小叶皮质和脾的动脉周围淋巴鞘增厚,380天胸腺皮质明显厚于对照组。结论:蜂花粉可明显促进蛋鸡免疫器官早期发育,延缓中枢免疫器官的退化。

关键词：蜂花粉/药理学脾/药物作用胸腺/药物作用鸡

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Immunohistochemical characterization of macrophage and dendritic cell subpopulations of the spleen, thymus, tongue and heart in cyclophosphamide-induced immunosuppressed rat

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ANATOMIA HISTOLOGIA EMBRYOLOGIA 2003年第2期32卷 80-88页

作者： Yoon, S Yoo, HJ Shim, NR Baek, SY Kim, BS Kim, JB Jun, EJ Son, YK Lee, SY Yoo, YH Pusan Natl Univ Dept Anat Coll Med Pusan 602739 South Korea

This study was undertaken to investigate the immunohistochemical characterization of different subpopulations of macrophages and dendritic cells (DCs) of the spleen, thymus, tongue and heart in cyclophosphamide (CY)-induced immunosuppressed rat. After CY treatment, remarkably, ED1(+), ED2(+) and ED3(+) macrophage subpopulations, in general, exhibited signs of cellular activation such as an increase in number and size of cell, and an upregulation of the ED1, ED2 and ED3 reactive surface molecule expression in all the organs studied, except for some macrophage subpopulations including ED1(+) macrophages in the non-lymphoid tissues. Subpopulations of DCs showed a differential sensitivity to CY. Lymphoid DCs were more sensitive to CY than non-lymphoid interstitial DCs. CY induced a conspicuous upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in the vascular endothelial cells, splenic marginal zone and thymic cortex. In this study, we demonstrated the in vivo effects of CY treatment on subpopulations of macrophages and DCs as well as on ICAM-1 expression in the rat spleen, thymus, tongue and heart. Moreover, our results shed more light on the activation effects of CY on certain subpopulations of macrophages, on the differential sensitivity of DCs to CY between the immature and mature ones, on the functional role of different subpopulations of macrophages, and on the significance of upregulated ICAM-1 expression in the splenic marginal zone and thymic cortex after CY treatment.

关键词：环磷酰胺/药理学树突细胞/分类树突细胞/药物作用树突细胞/免疫学免疫组织化学/兽医学免疫抑制剂/药理学胞间黏附分子1/生物合成巨噬细胞/分类巨噬细胞/药物作用巨噬细胞/免疫学心肌/细胞学大鼠 Sprague-Dawley 脾/细胞学脾/药物作用胸腺/细胞学胸腺/药物作用舌/细胞学舌/药物作用动物男(雄)性大鼠

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Protease-activated receptor-2 signaling triggers dendritic cell development

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AMERICAN JOURNAL OF PATHOLOGY 2003年第6期162卷 1817-1822页

作者： Fields, RC Schoenecker, JG Hart, JP Hoffman, MR Pizzo, SV Lawson, JH Duke Univ Med Ctr Dept Surg Durham NC 27710 USA Duke Univ Med Ctr Dept Pathol Durham NC 27710 USA Duke Univ Med Ctr Dept Immunol Durham NC 27710 USA

Dendritic cells (DC) are potent antigen-presenting cells that govern the effector cell. responses of the immune system. DC are thought to continuously develop from circulating progenitors in a process that is accelerated by inflammatory stimuli. However, the physiological signals that regulate the development of DC from precursor cells have not been well defined. Here we show that a serine protease acting via protease-activated receptor-2 (PAR-2) stimulates the development of DC from bone marrow progenitor cells cultured in granulocyte-macrophage colony-stimulating factor and IL-4. DC fail to develop in bone marrow cultures treated with soy bean trypsin inhibitor, a serine protease inhibitor, but this inhibition is overcome by a PAR-2 agonist peptide. DC do not spontaneously develop from the bone marrow of PAR-2-deficient mice, but can be stimulated to do so by inflammatory mediators. These results suggest that endogenous serine proteases stimulate DC development in vitro. Thus, serine proteases may help trigger adaptive immune responses in vivo.

关键词：抗原 CD11c/生物合成骨髓细胞/细胞学骨髓细胞/药物作用细胞分裂/药物作用细胞分裂/生理学细胞培养的树突细胞/细胞学树突细胞/药物作用树突细胞/代谢流式细胞术基因型粒细胞巨噬细胞集落刺激因子/药理学组织相容性抗原Ⅱ类/生物合成白细胞介素4/药理学小鼠近交C57BL 小鼠基因敲除寡肽类/药理学受体 PAR-2 受体凝血酶/激动剂受体凝血酶/遗传学受体凝血酶/生理学信号传导/生理学脾/细胞学脾/药物作用胰蛋白酶抑制剂 Kunitz大豆/药理学肿瘤坏死因子α/药理学动物女(雌)性男(雄)性小鼠

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Peptide-directed suppression of a pro-inflammatory cytokine response

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第22期275卷 16774-16778页

作者： Liu, XY Robinson, D Veach, RA Liu, D Timmons, S Collins, RD Hawiger, J Vanderbilt Univ Sch Med Dept Microbiol & Immunol Nashville TN 37232 USA Vanderbilt Univ Sch Med Dept Pathol Nashville TN 37232 USA

Signal-dependent nuclear translocation of transcription factor nuclear factor kappa B (NF-kappa B) is required for the activation of downstream target genes encoding the mediators of immune and inflammatory responses. To inhibit this inducible signaling to the nucleus, we designed a cyclic peptide (cSN50) containing a cell-permeable motif and a cyclized form of the nuclear localization sequence for the p50-NF-kappa B1 subunit of NF-kappa B. When delivered into cultured macrophages treated with the pro-inflammatory agonist lipopolysaccharide, cSN50 was a more efficient inhibitor of NF-kappa B nuclear import than its linear analog. When delivered into mice challenged with lipopolysaccharide, cSN50 potently blocked the production of proinflammatory cytokines (tumor necrosis factor alpha and interferon gamma) and significantly reduced the lethality associated with ensuing endotoxic shock. Based on specificity studies conducted with a mutated form of cSN50, a functional nuclear localization motif is required for this protective effect. Taken together, our findings demonstrate effective targeting of a cell-permeable peptide that attenuates cytokine signaling in vivo. This new class of biological response modifiers may be applicable to the control of systemic inflammatory reactions.

关键词：氨基酸序列细胞培养的细胞因子类/拮抗剂和抑制剂细胞因子类/生理学炎症介导素类/拮抗剂和抑制剂炎症介导素类/生理学脂多糖类/药理学巨噬细胞/药物作用巨噬细胞/代谢膜蛋白质类/血液膜蛋白质类/化学膜蛋白质类/药理学分子序列数据 NF-κB/拮抗剂和抑制剂肽类/血液肽类/化学肽类/药理学肽类环/血液肽类环/化学肽类环/药理学脾/细胞学脾/药物作用脾/代谢动物小鼠

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Mixed-function oxygenases, oxidative stress, and chromosomal damage measured in lesser scaup wintering on the Indiana Harbor Canal

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ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2000年第4期38卷 522-529页

作者： Custer, TW Custer, CM Hines, RK Sparks, DW Melancon, MJ Hoffman, DJ Bickham, JW Wickliffe, JK US Geol Survey Div Biol Resources Upper Midwest Environm Sci Ctr La Crosse WI 54603 USA US Fish & Wildlife Serv Bloomington IN 47403 USA US Geol Survey Div Biol Resources Patuxent Wildlife Res Ctr Laurel MD 20708 USA Texas A&M Univ Dept Wildlife & Fisheries College Stn TX 77843 USA Texas Tech Univ Dept Biol Sci Lubbock TX 79409 USA

During the winter of 1993-1994, male lesser scaup (Aythya affinis) were collected on the heavily polluted Indiana Harbor Canal, East Chicago, Indiana, and examined for several bioindicators of chemical exposure. Livers were analyzed for activities of three cytochrome P450-associated monooxygenases and four measures of oxidative stress. Blood and spleen were analyzed by flow cytometry for chromosomal damage. In a concurrent study, scaup tissues were analyzed for organic and inorganic contaminants. Ethoxyresorufin-O-dealkylase (EROD) activity in livers of scaup collected in January 1994 was significantly higher than in livers of scaup collected in March 1994 or in livers of reference birds. Three hepatic monooxygenase activities were each significantly correlated with polycyclic aromatic hydrocarbon (PAH) concentrations in scaup carcasses. Thiobarbituric acid (TBA) activity in scaup livers was positively correlated with iron, boron, and lead concentrations in livers and polychlorinated biphenyl concentrations in carcasses. TBA activity was negatively correlated with protein-bound thiol activity and mercury concentrations in livers. The coefficient of variation of DNA content in scaup blood cells was correlated with PAH concentrations in scaup carcasses. This is the first field study with birds to demonstrate a correlation between liver monooxygenase activity and carcass PAH concentrations and to show a direct correlation between PAH concentrations in tissues and somatic chromosomal damage in blood.

关键词：动物野生血细胞/药物作用细胞色素P450酶系统/代谢 DNA/分析 DNA损伤鸭/代谢环境暴露/分析流式细胞术淡水危害物质/分析危害物质/毒性印第安纳微粒体肝/药物作用微粒体肝/酶学氧化性应激/药物作用季节脾/细胞学脾/药物作用痕量元素/分析痕量元素/毒性水污染物化学性/分析水污染物化学性/毒性动物女(雌)性男(雄)性

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Synthesis and immunosuppressive activity of novel prodigiosin derivatives

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JOURNAL OF MEDICINAL CHEMISTRY 2000年第13期43卷 2557-2565页

作者： D'Alessio, R Bargiotti, A Carlini, O Colotta, F Ferrari, M Gnocchi, P Isetta, A Mongelli, N Motta, P Rossi, A Rossi, M Tibolla, M Vanotti, E Pharmacia & Upjohn SpA Discovery Res Oncol Dept Chem I-20014 Neviano MI Italy Pharmacia & Upjohn SpA Discovery Res Oncol Dept Pharmacol I-20014 Neviano MI Italy

Prodigiosins (Ps) represent a family of naturally occurring red pigments characterized by a common pyrrolylpyrromethene skeleton. Some members of this family have been shown to possess interesting immunosuppressive properties exerted with a novel mechanism of action, different from that of currently used drugs. In fact, Ps inhibit phosphorylation and activation of JAK-3, a cytoplasmic tyrosine kinase associated with a cell surface receptor component called common gamma-chain, which is exclusive of all IL-2 cytokine family receptors. Blocking common gamma-chain transduction activity results in a potent and specific immunosuppressive activity. With respect to the interesting and unexploited immunomodulating properties of this family of compounds we initiated a medicinal chemistry program aimed at finding novel prodigiosin derivatives with improved immunosuppressive activity and lower toxicity. Utilizing an unprecedented and flexible way of assembling the prodigiosin frame, a number of new derivatives have been prepared and tested leading to the choice of 4-benzyloxy-5-[(5-undecyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi-1H-pyrrole (PNU-156804, 16) as a lead immunosuppressant.

关键词：细胞存活/药物作用超敏反应迟发型/药物疗法免疫抑制剂/化学合成免疫抑制剂/化学免疫抑制剂/药理学免疫抑制剂/毒性淋巴细胞/细胞学淋巴细胞/药物作用小鼠近交C57BL 灵菌红素/类似物和衍生物灵菌红素/化学合成灵菌红素/化学灵菌红素/药理学灵菌红素/毒性吡咯类/化学合成吡咯类/化学吡咯类/药理学吡咯类/毒性脾/细胞学脾/药物作用构效关系肿瘤细胞培养的动物女(雌)性人类小鼠

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Suppression of rat and mouse lymphocyte function by urban air particulates (Ottawa dust) is reversed by N-acetylcysteine

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JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A 2000年第2期59卷 67-85页

作者： Omara, FO Fournier, M Vincent, R Blakley, BR Univ Quebec INRS Inst Armand Frappier Sante Humaine Ctr Rech Sante Humaine Pointe Claire PQ H9R 1G6 Canada Hlth Canada Environm Hlth Directorate Ottawa ON K1A 0L2 Canada Univ Saskatchewan Dept Vet Physiol Sci Saskatoon SK S7N 0W0 Canada

Epidemiology studies have demonstrated increased pulmonary morbidity such as allergy and infection with episodes of high particulate air pollution (size range 0.1-10 mu m diameter, PM10), but the mechanism(s) for this association is not yet well defined. The present study was undertaken to evaluate the effects of EHC-93 urban particles (Ottawa dust) on immune functions of peripheral blood mononuclear cells (PBMCs) and splenocytes from male Fischer 344 rats and C57Bl/6 mice. Immune function endpoints evaluated included cell viability, lymphocyte blastogenesis stimulated by T-cell mitogen (concanavalin A, Con A) or B-cell mitogens [lipopolysaccharide (LPS) or LPS/dextran sulfate], intracellular Ca2+ concentration, interleukin 2 (IL-21 production, and expression of receptors for transferrin (TfR) and IL-2 (IL-2R). In addition, the effect of N-acetylcysteine (NAC), an antioxidant, on the toxicity of EHC-93 particles was evaluated Total EHC-93 particles, water leachate of EHC-93, and washed EHC-93 suppressed proliferation of PBMCs and splenocytes to T- and B-cell mitogens. Treatment of splenocytes with EHC-93 particles did nor alter intracellular Ca2+ concentration or mitogen-induced expression of TfR and IL-2R expression, bur increased IL-2 production assayed by enzyme-linked immunosorbent assay (ELISA). in spire of an increase in IL-2 production, exogenous IL-2 when added to cultures was able to reverse the suppression of Con A-induced lymphocyte proliferation by EHC-93 particles. Furthermore, the suppressive effect of EHC-93 particles on mitogen-induced lymphocyte proliferation was completely abolished by addition of the antioxidant NAC to cultures, suggesting a possible role of oxidative factors for the toxicity Of EHC-93 particles.

关键词：乙酰半胱氨酸/激动剂乙酰半胱氨酸/药理学空气污染物/拮抗剂和抑制剂空气污染物/毒性钙/代谢细胞存活/药物作用细胞培养的粉尘自由基清除剂/激动剂自由基清除剂/药理学白细胞介素2/代谢白细胞介素2/药理学淋巴细胞活化/药物作用淋巴细胞/药物作用淋巴细胞/免疫学小鼠近交C57BL 安大略大鼠近交F344 受体白细胞介素2/代谢受体转铁蛋白/代谢脾/细胞学脾/药物作用脾/免疫学动物男(雄)性小鼠大鼠

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Identification of R146225 as a novel, orally active inhibitor of interleukin-5 biosynthesis

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期295卷 655-661页

作者： Van Wauwe, J Aerts, F Cools, M Deroose, F Freyne, E Goossens, J Hermans, B Lacrampe, J Van Genechten, H Van Gerven, F Van Nyen, G Janssen Res Fdn B-2340 Beerse Belgium

Interleukin (IL)-5 regulates the growth, differentiation, and activation of eosinophils. When activated, eosinophils release an array of proinflammatory and cytotoxic products and act as prominent effector cells in the process of allergic inflammation. Depriving eosinophils of IL-5 may therefore represent a viable approach to treat allergic disorders. This study describes the identification of R146225, a novel six-substituted azauracil derivative, as a potent, orally active inhibitor of IL-5 biosynthesis, capable of reducing pulmonary eosinophilia in mice. In vitro, R146225 inhibited IL-5 protein formation by activated human whole blood (IC50 = 34 nM), human peripheral blood mononuclear cells (IC50 = 24 nM), and murine spleen cells (IC50 = 6 nM). In contrast, the compound enhanced generation of interferon-gamma and had little or no inhibitory effect on the production of IL-2 and IL-4. Reverse transcription-polymerase chain reaction analysis of stimulated whole blood cells indicated R146225's ability to down-regulate IL-5 mRNA expression. In vivo p.o. administration of R146225 (2.5 mg/kg) to mice before an i.v. anti-CD3 antibody challenge reduced IL-5 but enhanced interferon-gamma serum levels, without affecting IL-2 and IL-4 production. Analogous to the in vitro results, R146225 suppressed splenic IL-5 mRNA expression, while message levels of the other cytokines remained unchanged. Moreover, p.o. dosing of R146225 (0.6-2.5 mg/kg) dose dependently reduced the pulmonary accumulation of eosinophils induced in mice by an intranasal instillation of Cryptococcus neoformans. Based on these data, R146225 may be useful in the therapy of eosinophil-driven allergic conditions.

关键词：投药口服隐球菌病/药物疗法隐球菌病/病理学嗜酸细胞/药物作用嗜酸细胞/病理学干扰素γ/生物合成干扰素γ/血液白细胞介素2/生物合成白细胞介素2/血液白细胞介素4/生物合成白细胞介素4/血液白细胞介素5/拮抗剂和抑制剂白细胞介素5/生物合成白细胞介素5/血液白细胞单核/药物作用白细胞单核/代谢小鼠近交BALBC 小鼠近交C57BL 肺嗜酸粒细胞增多/药物疗法肺嗜酸粒细胞增多/微生物学肺嗜酸粒细胞增多/病理学嘧啶类/药理学 RNA 信使/生物合成脾/细胞学脾/药物作用脾/代谢三嗪类/药理学成年人动物女(雌)性人类小鼠

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