背景:Syndecan-1是在血管内皮细胞的糖萼中发现的硫酸乙酰肝素蛋白聚糖。syndecan-1的血清水平已被反复证明在创伤和休克后增加,但目前尚不清楚syndecan-1是否在炎症反应中起积极作用或仅仅是低灌注状态的生物标志物.这项研究的目的是确定在没有创伤的情况下,syndecan-1在炎症过程中的作用。
方法:将雄性小鼠随机分为5组(n=3)。四组接受浓度增加的syndecan-1(每血体积1、10、100和1000pg/mL),第五组通过静脉注射给予生理盐水作为对照。这些浓度是基于先前的syndecan-1酶联免疫吸附测定数据选择的,所述数据在小鼠中诱导出血性休克后获得,导致血清水平为10-6000pg/mL。在1-4-,和24小时时间点用于血清生物标志物评估。进行了多重酶联免疫吸附测定以分析促炎细胞因子和趋化因子,包括白细胞介素(IL)-1a,IL-1b,IL-2、IL-3、IL-4、IL-6、IL-10、IL-12、IL-17、单核细胞趋化蛋白-1、TNF-α、巨噬细胞炎性蛋白-1α,粒细胞-巨噬细胞集落刺激因子,和正常T细胞表达和推测分泌水平。在以1000pg/mL给药syndecan-1的单独小鼠组中通过旋转血栓弹性测定法分析全血,并在1小时与假小鼠进行比较。
结果:与假动物相比,在1000pg/mL组中肿瘤坏死因子-α显著升高。IL-1a无明显变化,IL-1b,IL-2,IL-3,IL-4,IL-6,IL-10,IL-12,单核细胞趋化蛋白-1,巨噬细胞炎性蛋白-1α,粒细胞-巨噬细胞集落刺激因子,与仅接受盐水的小鼠相比,任何组的正常T细胞在1、4和24小时表达并可能分泌。在1000pg/mLsyndecan-1组和shams之间的凝血能力在1小时时没有显着差异。结论:在任何时间点,小鼠体内炎性细胞因子浓度均未随着syndecan-1剂量的增加而变化,除了短暂的肿瘤坏死因子-α的急性变化。根据我们的结果,syndecan-1似乎是炎症的生物标志物,而不是引发炎症反应的积极参与者.进一步的研究将集中在失血性休克后syndecan-1的作用。
BACKGROUND: Syndecan-1 is a heparan sulfate proteoglycan found in the glycocalyx of vascular endothelial cells. Serum levels of syndecan-1 have repeatedly been demonstrated to increase following traumatic injury and shock, but it is unclear whether syndecan-1 plays an active role in the inflammatory response or is simply a biomarker of a state of hypoperfusion. The aim of this study was to identify the role of syndecan-1 role in the inflammatory process in the absence of trauma.
METHODS: Male mice were randomized into five groups (n = 3). Four groups received increasing concentrations of syndecan-1 (1, 10, 100, and 1000pg/mL per blood volume) and a fifth group was given normal saline as a control via intravenous injection. These concentrations were selected based on previous syndecan-1 enzyme-linked immunosorbent assay data acquired following induced hemorrhagic shock in mice resulting in serum levels of 10-6000 pg/mL. Mice from each group were sacrificed at 1-, 4-, and 24-h time points for serum biomarker evaluation. A multiplex enzyme-linked immunosorbent assay was performed to analyze proinflammatory cytokines and chemokines including interleukin (IL)-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemoattractant protein-1, TNF-α, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, and normal T cell expressed and presumably secreted levels. Whole blood was analyzed via rotational thromboelastometry in a separate group of mice dosed with syndecan-1 at 1000 pg/mL and compared to sham mice at 1 h.
RESULTS: Tumor necrosis factor-α was significantly elevated in the 1000 pg/mL group compared to sham animals. There were no significant changes in IL-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, monocyte chemoattractant protein--1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, or normal T cell expressed and presumably secretedat 1, 4, and 24 h for any group when compared to mice receiving saline alone. No significant differences were noted in coagulability between the 1000 pg/mL syndecan-1 group and shams at 1 h CONCLUSIONS: Inflammatory cytokine concentrations did not change with increasing dosage of syndecan-1 within mice at any timepoint, except for an acute change in tumor necrosis factor-α which was transient. Based on our results, syndecan-1 appears to be a biomarker for inflammation rather than an active participant in eliciting an inflammatory response. Further research will focus on the role of syndecan-1 following hemorrhagic shock.