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Long-term dynamic profiling of inflammatory mediators in double-hit burn and sepsis animal models

机译:在双发烧伤和败血症动物模型中炎症介质的长期动态分布

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Burn injuries together with its subsequent complications, mainly bacterial infections originating from gastrointestinal tract, activate the host immune system through stimulation of a series of local and systemic responses, including the release of inflammatory mediators. To gain a more comprehensive understanding of these complex physiological changes and to propose therapeutic approaches to combat the deleterious consequences of burn and septic shocks, it is essential to analyze animal models of burn and sepsis. In this study, we analyzed the long term profiles of cytokines and chemokines in rat models which received burn injury followed 2 days later by cecal ligation and puncture (CLP) to induce sepsis and were sacrificed at different time points within 10. days (0, 1, 2, 3, 4, 7 and 10. days). It was observed that MCP-1 concentrations were elevated in all animal models following the burn injury or CLP treatment. IP-10 concentration was persistently decreased after CLP or sham-CLP treatments. GRO/KC concentration was also increased following the burn injury and CLP. It was elucidated that, in more severe injury model which received both burn and CLP treatments, GMCSF and MIP-1α (chemokines), IL-1α (a pro-inflammatory cytokine) and IL-6 (exhibiting both pro- and anti-inflammatory behaviors) were upregulated on the 7th and 10th days, which might be to protect the host system from the subsequent complications caused by burn and sepsis. In order to elucidate critical regulatory interactions, putative transcription factors of the inflammatory mediators which have been significantly changed following the injuries were further identified by analyzing the conserved regions of the promoters of cytokines and chemokines. In conclusion, the long term profiles of the inflammatory mediators were profoundly characterized in this study to gain a comprehensive understanding of inflammatory mediators' behaviors in various injury models.
机译:烧伤及其后续并发症(主要是胃肠道细菌感染)通过刺激一系列局部和全身反应(包括释放炎性介质)来激活宿主免疫系统。为了更全面地了解这些复杂的生理变化,并提出治疗方法以对抗烧伤和败血性休克的有害后果,分析烧伤和败血症的动物模型至关重要。在这项研究中,我们分析了大鼠模型的细胞因子和趋化因子的长期概况,该模型在遭受烧伤后2天后进行盲肠结扎和穿刺(CLP)诱导败血症,并在10天之内在不同时间点处死(0, 1、2、3、4、7和10天)。观察到,在烧伤或CLP处理后的所有动物模型中,MCP-1浓度均升高。 CLP或假CLP处理后IP-10浓度持续降低。烧伤和CLP后GRO / KC浓度也增加。已阐明,在同时接受烧伤和CLP治疗的更严重的损伤模型中,GMCSF和MIP-1α(趋化因子),IL-1α(促炎细胞因子)和IL-6(均显示促炎和抗炎)行为)在第7天和第10天上调,这可能是为了保护宿主系统免于因烧伤和败血症引起的后续并发症。为了阐明关键的调节相互作用,通过分析细胞因子和趋化因子启动子的保守区域,进一步鉴定了在损伤后已显着改变的炎性介质的假定转录因子。总之,本研究深刻表征了炎症介质的长期概况,以全面了解各种损伤模型中炎症介质的行为。

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