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内毒素信号转导机制的研究进展 总被引：3，自引：0，他引：3
细菌内毒素即脂多糖 (LPS)可激活单核 /巨噬细胞 ,产生一系列炎症反应 ,而LPS跨膜信号转导是引起细胞效应的关键。本文主要综述LPS结合蛋白 (LBP)、LPS受体 (mCD1 4、sCD1 4 )、Toll样受体 2、 4 (TLR2、TLR4)以及清道夫受体 (SR)、β2 整合素 ,L selectin在LPS激活细胞及信号跨膜传递中的重要作用。另外 ,对LPS介导的细胞内信号转导机制也进行了综述。深入研究LPS信号转导的分子机制 ,可望为有效控制内毒素所引起的一系列炎症反应及机体损伤提供新思路 相似文献
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内毒素的信号转导 总被引：3，自引：1，他引：2
内毒素即脂多糖介导的细胞信号转导在激活靶细胞产生一系列应答反应，导致机体损伤并出现病理变化中起着关键作用。LPS信号转导涉及到多种血清蛋白和受体，如LBP、sCD14,mCD14，以及CD11/CD18，LBP/CD14系统在LPS信号转导中起着重要作用，但并非LPS信号转导所必需的LPS与受体结合后，细胞内信号转导涉及到酪氨酸激酶与MAPK超家族，通过多个MAPK通路和保守的三级激酶级联反应（MAPKKK-MAPKK-MAPK）将LPS信号转导致胞内，引起细胞应答，同时p38MAPK对LPS介导的细胞反应有重要调节作用，这些均表明，LPS信号转导可能是一个多受体，多通路，可调控的复杂过程。 相似文献
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内毒素（endotoxin,ET）是大多数革兰氏阴性菌(G^-)细胞壁的结构成分,主要来自该类细菌细胞壁外膜的脂多糖(Lipopolysaccharide,LPS)成分,此外,鲜见于革兰氏阳性细菌和真菌,当细菌裂解时,ET可被释放出来,尤其是细菌在快速生长或死亡时,最有利于ET的释放。ET的一般特性是耐热,对人和动物有致热性,无特异性,能引起实验动物局部或全身的Shwartzman反应,具有溶瘤作用等。通常机体内肠道中可存在大量的内毒素,但在正常情况下并不产生损害．只有当细菌产生的内毒素进入肠道组织和血液才能引起疾病。 相似文献
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内毒素增强血管渗透血浆白蛋白的能力是已知的。然而,这种增强是否由于毒素的直接作用或血管活性胺、激肽或其他物质的一种高循环水平所致,现在仍然是不清楚的。我们以前报导过多核白细胞在试管内释放血管渗透性因子和内源性热原质(白细胞热原质)。在炎症和发热反应中,多核白细胞确起有重要作用。本次研究的目的是调查内毒素引起的发热反应期间家兔血液中血管渗透性因子的出现情况。 相似文献
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内毒素对血管内皮细胞的损伤是多种疾病包括大肠杆菌病致病的根本原因,能介导多种细胞,特别是激活单核巨噬细胞,使其合成和释放各种细胞因子,再通过旁分泌或体循环作用于其它组织细胞,引起全身炎症反应综合征,严重者导致休克、多器官功能衰竭和死亡.虽然现在预防和治疗内毒素损伤的方法和途径多种多样,但还没有一种非常有效的手段.而作为天然物品的中药,有很多种类可以抗内毒素损伤,并且具有低毒低副作用等优点,有可能成为今后防治内毒素损伤的重要研究方向. 相似文献
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内毒素是构成革兰氏阴性杆菌细胞壁外膜,分子量约为10~8左右的类脂多糖体(LPS.Lipopolysaccharide).它具有使体温升高,白细胞减少,激活补体系统和凝固系统引起血管内弥漫性凝血(DIC),休克,死亡等多种生 相似文献
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内毒素（endotoxin）是革兰氏阴性细菌（gram negative bacillus，GNB）死亡时裂解出来的细胞壁脂多糖（1ipopolysaccharide，LPS）成分。LPS的基本结构由0一特异性抗原多糖、核心多糖和类脂A（1ipidA）三部分组成，其中lipidA是内毒素的生物学活性主要毒性成分。当进入动物体内的内毒素超过一定限量后，可触发体内一系列病理、生理过程，引起发热、休克、弥散性血管内凝血和多器官功能性衰竭，以致死亡。由于内毒素具有稳定性强、致死率高等特点，因此，研制高亲和力、能中和内毒素且毒性低的药物具有重要的意义。本文就近年来抗内毒素蛋白及多肽方面的研究进行综述。 相似文献
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内毒素增敏系统LBP/CD14在动物疾病中的研究现状 总被引：1，自引：0，他引：1
小剂量的细菌内毒素(简称内毒素)对机体有一定的益处,但当超过这个剂量时,内毒素增敏系统将会被激活,进行内毒素信号的转导,诱导机体产生大量炎症介质,破坏机体内外环境的平衡,产生一系列的不良反应,从而损害动物的组织,导致全身炎症反应综合征(SIRS)和脓毒血症等严重的临床综合征,甚至死亡,给养殖业造成大的经济损失。文章从分子水平探讨内毒素增敏系统(包括LBP/CD14、膜组织伸展钉蛋白、钟样受体4、白细胞整合素CD11/CD18等)在动物机体内受到内毒素攻击时的变化及意义,以及内毒素在体内的信号传导过程,以期给畜牧兽医工作者提供一些关于内毒素方面的进展。 相似文献
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Regulation of the growth hormone and luteinizing hormone response to endotoxin in sheep 总被引：4，自引：0，他引：4
Infectious disease processes cause physiological adaptations in animals to reorder nutrient partitioning and other functions to support host survival. Endocrine, immune and nervous systems largely mediate this process. Using endotoxin injection as a model for catabolic disease processes (such as bacterial septicemia), we have focused our attention on regulation of growth hormone (GH) and luteinizing hormone (LH) secretion in sheep. Endotoxin produces an increase in plasma GH and a decrease in plasma LH concentrations. This pattern can be reproduced, in part, by administration of various cytokines. Antagonists to both interleukin-1 (IL-1) and tumor necrosis factor (TNF) given intravenously (IV) prevented the endotoxin-stimulated increase in GH. Since endotoxin will directly stimulate GH and LH release from cultured pituitary cells, the data suggest a pituitary site of action of the endotoxin to regulate GH. Studies with portal vein cannulated sheep indicated that gonadotropin releasing hormone was inhibited by endotoxin, suggesting a central site of action of endotoxin to regulate LH. However, other studies suggest that endotoxin may also regulate LH secretion at the pituitary. Thus, IL-1 and TNF regulate GH release from the pituitary gland while endotoxin induces a central inhibition of LH release. 相似文献
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Schroeder EL Holcombe SJ Cook VL James MD Gandy JC Hauptman JG Sordillo LM 《Equine veterinary journal》2011,43(3):341-347
Reasons for performing the study: Endotoxaemia causes substantial morbidity and mortality in horses with colic and sepsis. Ethyl pyruvate is a novel anti‐inflammatory medication that improved survival in preclinical models of severe sepsis endotoxaemia and intestinal ischaemia and reperfusion in rodents, swine, sheep and dogs and may be a useful medication in horses. Hypothesis: Ethyl pyruvate has no adverse effects in normal horses and is biologically active based on suppression of proinflammatory gene expression in endotoxin stimulated whole blood, in vitro. Methods: Physical and neurological examinations, behaviour scores, electrocardiograms and clinicopathological tests were performed on 5 normal healthy horses receiving 4 different doses of ethyl pyruvate. Doses included 0, 50, 100 and 150 mg/kg bwt administered in a randomised crossover design with a 2 week washout period between doses. Biological efficacy was assessed by stimulating whole blood with endotoxin from the horses that received ethyl pyruvate prior to and 1 and 6 h after drug infusion. Gene expression for TNFα, IL‐1β and IL‐6 was assessed. Results: There were no effects of drug or dose (0, 50, 100 or 150 mg/kg bwt) on any of the physical or neurological examination, behaviour factors, electrocardiogram or clinical pathological results collected from any of the horses. All parameters measured remained within the normal reference range. There was a significant reduction in TNFα, IL‐1β and IL‐6 gene expression in endotoxin stimulated whole blood from horses 6 h after receiving 150 mg/kg bwt ethyl pyruvate. There were no detectable effects on gene expression of any of the other doses of ethyl pyruvate tested. Conclusion: We were unable to detect any detrimental effects of ethyl pyruvate administration in normal horses. Ethyl pyruvate significantly decreased proinflammatory gene expression in endotoxin stimulated blood 6 h after drug administration. Clinical relevance: Ethyl pyruvate may be a safe, effective medication in endotoxaemic horses. 相似文献
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A S van Miert C T van Duin J H Verheijden A J Schotman 《Research in veterinary science》1982,33(2):248-255
Flurbiprofen, a potent non-steroidal anti-inflammatory and antipyretic agent, was given as an intravenous infusion (2 mg/kg) followed by a bolus injection of 1 mg/kg six hours later. After drug administration body temperature and rumen contractions were slightly depressed, whereas urea values gradually increased; serum sorbitol dehydrogenase (SDH) activity, plasma iron concentration and the number of circulating lymphocytes were significantly lower. Intravenous injection of endotoxin from Escherichia coli O111B4 (0.1 microgram/kg) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophylic leucocytosis, changes in urea values, hypoferraemia, hypozincaemia and a decline in serum alkaline phosphatase (ALP) activity, whereas gamma-glutamyltranspeptidase, glutamic oxalacetic transaminase, lactic dehydrogenase and SDH values were not significantly altered. Pretreatment with flurbiprofen completely abolished the febrile reactions to endotoxin. The endotoxin-induced inhibition of rumen contractions was only delayed. The drug blocked the initial tachycardia to endotoxin but did not prevent the secondary biphasic increase in heart rate. Flurbiprofen failed to modify the endotoxin-induced decrease in both plasma zinc and serum ALP activity whereas the decline in plasma iron concentration was delayed. After drug pretreatment the changes in circulating white blood cells were more pronounced. These data demonstrate that most of the haematological, blood biochemical and clinical effects of endotoxin cannot be blocked by flurbiprofen, and that these effects are not due to the increase in body temperature alone. Tolerance induced by repetitive daily intravenous administration of endotoxin resulted in an almost complete abolition of all the effects. However, the plasma iron values from tolerant goats were significantly lower than those from non-tolerant animals, which demonstrates that the development of a refractory state can result in modification of this biochemical parameter. 相似文献
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Thromboxane A2 may play a major role in circulatory shock. In some species, thromboxane synthetase inhibitors have a beneficial effect on shock induced by endotoxin, trauma, sepsis and administration of arachidonate. In some shock models, however, results with thromboxane synthetase inhibitors have been conflicting. The effect of UK-38,485, a selective thromboxane inhibitor, was evaluated in ponies injected with endotoxin intraperitoneally. Four groups of ponies were used to compare the effects of endotoxin alone, UK-38,485 alone, treatment with UK-38,485 before endotoxin challenge and treatment with UK-38,485 after endotoxin challenge. Haematological, metabolic, eicosanoid and clinical responses in each group were evaluated. The results indicated that UK-38,485 is an effective inhibitor of thromboxane A2 generation following endotoxin challenge. Prostacyclin values were elevated compared with baseline in ponies administered UK-38,485 and endotoxin. However, prostacyclin values were not significantly different from those of ponies receiving endotoxin alone. Furthermore, UK-38,485 failed to attenuate the haematological, metabolic and clinical manifestations commonly seen in the pony after endotoxin challenge. 相似文献
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Berndt A Derksen FJ Edward Robinson N 《Veterinary journal (London, England : 1997)》2010,183(1):54-57
Inflammatory airway disease is common in stabled horses, with a prevalence of 17.3% in Michigan pleasure horses. Stable dust is rich in endotoxin, which may induce neutrophilic airway inflammation. Climatological conditions (ambient temperature and relative humidity) may influence endotoxin concentrations in pastures. The aim of this project was to determine if endotoxin levels in the breathing zone of horses in stables were higher than of horses on pasture, and if the endotoxin on pasture was associated with climatological conditions. Endotoxin exposure of six horses that were stabled or on pasture was determined by a Limulus amebocyte lysate assay. Climatological data were obtained from the US National Climatic Data Center. Endotoxin exposure was significantly higher (about 8-fold) in stables than on pasture. On pasture, endotoxin varied widely, despite constant climatological conditions. It was concluded that stabled horses are exposed to higher endotoxin concentrations than horses on pastures. Local endotoxin concentrations may be more important than ambient climatological conditions in determining endotoxin exposure of individual horses. 相似文献
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P F Daels G H Stabenfeldt J P Hughes K Odensvik H Kindahl 《American journal of veterinary research》1991,52(2):276-281
The role of prostaglandin F2 alpha (PGF2 alpha) in embryonic loss following induced endotoxemia was studied in mares that were 21 to 44 days pregnant. Thirteen pregnant mares were treated with a nonsteroidal anti-inflammatory drug, flunixin meglumine, to inhibit the synthesis of PGF2 alpha caused by Salmonella typhimurium endotoxin given IV. Flunixin meglumine was administered either before injection of the endotoxin (group 1, -10 min; n = 7), or after endotoxin injection into the mares (group 2, 1 hour, n = 3; group 3, 2 hours, n = 3); 12 pregnant mares (group 4) were given only S typhimurium endotoxin. In group 4, the secretion of PGF2 alpha, as determined by plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations, was biphasic, initially peaking at 30 minutes followed by a second, larger peak approximately 105 minutes after the endotoxin was given IV. When flunixin meglumine was administered at -10 minutes, synthesis of PGF2 alpha was inhibited for several hours, after administration of flunixin meglumine at 1 hour, the second secretory surge of PGF2 alpha was blocked, and administration of the drug at 2 hours did not substantially modify the secretion of PGF2 alpha. Plasma progesterone concentrations were unchanged after endotoxin injections were given in group 1. In group 2, progesterone values decreased less than 2 ng/ml and remained low for several days. In group 3 and group 4, progesterone concentrations decreased to values less than 0.5 ng/ml by 48 hours after endotoxin injections were given.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Frellstedt L McKenzie HC Barrett JG Furr MO 《Veterinary immunology and immunopathology》2012,149(1-2):97-102
Endotoxemia is responsible for severe illness in horses. Individuals can become clinically unresponsive to the endotoxin molecule after an initial exposure; a phenomenon referred to as 'endotoxin tolerance' (ET). ET has been observed clinically in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMC) in vitro, and to describe selected cytokine responses which are associated with ET. ET was induced by culturing cells with three concentrations of endotoxin, and evaluated after a second dose of endotoxin given to challenge the cells. The relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative PCR. ET was induced in all cells exposed to the 2-step endotoxin challenge. The relative mRNA expression of IL-10 in tolerized cells was not different from positive control cells. In contrast, the relative mRNA expression of IL-12 in tolerized cells was decreased by 15-fold after the second endotoxin challenge. This experiment demonstrated a reliable method for the ex vivo induction of ET in equine PBMC. A marked suppression of IL-12 production is associated with ET. 相似文献
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《Domestic animal endocrinology》1998,15(5):305-308
There is good evidence for the interaction of neuroendocrine and immune systems. Endotoxin (LPS)-induced mediators (e.g., cytokines, prostaglandins etc) set on endocrine organs (e.g., the hypothalamo-pituitry-adrenal axis; thyroid glands etc). Endotoxin-treated, intestinal ischemic, or irradiated rats show decreased T4 levels of blood. These animals cannot respond to TSH because the TSH-receptors of follicular membranes are disturbed by LPS in the thyroid glands. Radiodetoxified endotoxin is an effective immunstimulator and does not disturb the follicular membrane of thyroid gland. Thus, the T4 production remains normal. The bile acids—as the end-product of cholesterol metabolism—play an important role in the physiological defense of macroorganisms against endotoxin and other lipid-like agents (Physico-chemical defense) and in the regulation of endocrine system, including the reproduction. 相似文献