Dexmedetomidine attenuates inflammation and organ injury partially by upregulating Nur77 in sepsis.
Dexmedetomidine attenuates inflammation and organ injury partially by upregulating Nur77 in sepsis.
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DOI：
10.1002/iid3.883
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发表时间：
2023-06
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本研究旨在探讨右美托咪定（Dex）对脓毒症患者炎症和器官损伤的影响，以及右美托咪定与核受体77 （Nur77）的潜在关系。我们研究了右美托咪定对盲肠结扎和穿刺（CLP）小鼠模型中脂多糖（LPS）诱导的RAW264.7细胞炎症和器官损伤的影响。此外，我们检查了右美托咪定和Nur77之间的关系。采用定量逆转录聚合酶链反应和western blot分析不同刺激方式下RAW264.7细胞中Nur77的表达水平。使用酶联免疫分析法评估细胞中的炎症细胞因子水平。通过检查肺、肝和肾的组织病理学来评估器官损伤。右美托咪定增加了LPS处理RAW264.7细胞中Nur77和IL - 10的表达，并下调了炎症因子（IL - 1β和TNF - α）。右美托咪定对LPS处理的RAW264.7细胞的炎症抑制作用通过过表达Nur77得到促进，而下调Nur77则被逆转。此外，右美托咪定促进了肺中Nur77的表达和CLP诱导的肺、肝和肾的病理改变。用激动剂Cytosporone B （CsnB）激活Nur77可显著抑制LPS处理的RAW264.7细胞中IL - 1β和TNF - α的产生。相反，在LPS处理的RAW264.7细胞中，敲低Nur77可增加IL - 1β和TNF - α的产生。右美托咪定可以减轻炎症和器官损伤，至少部分是通过上调败血症中的Nur77。右美托咪定通过上调败血症中的Nur77来减轻炎症和器官损伤。
The aim of this study was to investigate the effect of dexmedetomidine (Dex) on inflammation and organ injury in sepsis, as well as the potential relationship between Dex and nuclear receptor 77 (Nur77). We investigated the effects of dexmedetomidine on lipopolysaccharide (LPS)‐induced inflammation in RAW264.7 cells and organ injury in the cecal ligation and puncture (CLP) mouse model. Additionally, we examined the relationship between dexmedetomidine and Nur77. The expression levels of Nur77 in RAW264.7 cells were analyzed under various types of stimulation using quantitative reverse transcription polymerase chain reaction and western blot analysis. Inflammatory cytokine levels in the cells were evaluated using enzyme‐linked immunoassay. Organ injuries were assessed by examining tissue histology and pathology of the lung, liver, and kidney. Dexmedetomidine increased the expression of Nur77 and IL‐10, and downregulated inflammatory cytokines (IL‐1β and TNF‐α) in LPS‐treated RAW264.7 cells. The effect of dexmedetomidine on inhibiting inflammation in LPS‐treated RAW264.7 cells was promoted by overexpressing Nur77, while it was reversed by downregulating Nur77. Additionally, dexmedetomidine promoted the expression of Nur77 in the lung and CLP‐induced pathological changes in the lung, liver, and kidney. Activation of Nur77 with the agonist Cytosporone B (CsnB) significantly suppressed the production of IL‐1β and TNF‐α in LPS‐treated RAW264.7 cells. In contrast, knockdown of Nur77 augmented IL‐1β and TNF‐α production in LPS‐treated RAW264.7 cells. Dexmedetomidine can attenuate inflammation and organ injury, at least partially, via upregulating Nur77 in sepsis. Dexmedetomidine attenuates inflammation and organ injury by upregulating Nur77 in sepsis.