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幼鼠内毒素刺激后肺部和脾脏中(1,4)-α-D-葡聚糖的免疫反应。

Immunological response to (1,4)-alpha-D-glucan in the lung and spleen of endotoxin-stimulated juvenile rats.

机构信息

Division of Critical Care Medicine, Miami Children's Hospital, Miami, FL, USA.

出版信息

Basic Clin Pharmacol Toxicol. 2009 Nov;105(5):301-6. doi: 10.1111/j.1742-7843.2009.00447.x. Epub 2009 Jul 13.

Abstract

We investigated the effects of (1,4)-alpha-D-glucan (alpha-DG), a novel immune stimulatory drug from Tinospora cordifolia, on the concentration of pro- and anti-inflammatory cytokines (interleukin [IL]-1beta, IL-6, tumour necrosis factor-alpha [TNF-alpha], gamma-interferon [IFN-gamma] and IL-10) in the lung and spleen of endotoxin-stimulated juvenile rats. Experimental groups (n = 16/group) included controls with an intraperitoneal injection of saline, endotoxaemic rats with a non-lethal dose of 10 mg/kg Escherichia coli endotoxin, and endotoxaemic rats treated with two doses of 10 mg/kg alpha-DG, intraperitoneally, 2 and 4 hr after endotoxin injection. At 24 hr of treatment, rats were euthanized and lungs and spleen were removed for cytokines determination and lung injury. Endotoxaemia increased IL-1beta concentration by fivefold in both organs, while creating a moderate pulmonary hypercellularity (demonstrated by about 11% increase in the alveolar-septal thickening and 11% decrease in the alveolar-interstitial space ratio). In the lung, alpha-DG treatment reduced concentrations of IL-1beta by 30% (p > 0.05), IL-6 by 43% (p < 0.01), IFN-gamma by 46% (p < 0.01) and the anti-inflammatory cytokine, IL-10, by 31% (p > 0.05) compared to endotoxaemia. In the spleen, alpha-DG treatment decreased the ratio of IL-1beta to IL-10 by 55% (p < 0.05), demonstrating an anti-inflammatory trend. These data suggest that alpha-DG differentially modulates cytokine response in the lung and spleen and modifies the pro- and anti-inflammatory balance during an early period of endotoxaemia in juvenile rats.

摘要

我们研究了从穿心莲中提取的新型免疫刺激药物 1,4-α-D-葡聚糖(α-DG)对脂多糖刺激的幼年大鼠肺和脾中促炎和抗炎细胞因子(白细胞介素[IL]-1β、IL-6、肿瘤坏死因子-α[TNF-α]、γ-干扰素[IFN-γ]和 IL-10)浓度的影响。实验组(n=16/组)包括腹腔注射生理盐水的对照组、接受非致死剂量 10mg/kg 大肠杆菌脂多糖的内毒素血症大鼠组,以及腹腔注射两次 10mg/kgα-DG 的内毒素血症大鼠组,两次注射时间分别为内毒素注射后 2 小时和 4 小时。治疗 24 小时后,处死大鼠,取出肺和脾,用于细胞因子测定和肺损伤评估。内毒素血症使两个器官中的 IL-1β 浓度增加了 5 倍,同时导致肺组织中度细胞增生(肺泡-间隔增厚增加约 11%,肺泡-间质空间比降低 11%)。在肺组织中,与内毒素血症相比,α-DG 治疗使 IL-1β 浓度降低了 30%(p>0.05),IL-6 降低了 43%(p<0.01),IFN-γ 降低了 46%(p<0.01),抗炎细胞因子 IL-10 降低了 31%(p>0.05)。在脾组织中,α-DG 治疗使 IL-1β 与 IL-10 的比值降低了 55%(p<0.05),表明其具有抗炎趋势。这些数据表明,α-DG 可调节幼年大鼠内毒素血症早期肺和脾组织中的细胞因子反应,并调节促炎和抗炎平衡。

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