Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain injury
Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain injury
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DOI：
10.1016/j.neulet.2016.11.047
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发表时间：
2017-04
影响因子：
2.5
通讯作者：
Yafei Li;Xihong Li;Y. Qu;Jichong Huang;T. Zhu;F. Zhao;Shiping Li;D. Mu
中科院分区：
文献类型：
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作者：
Yafei Li;Xihong Li;Y. Qu;Jichong Huang;T. Zhu;F. Zhao;Shiping Li;D. Mu
高迁移率组 Box-1 (HMGB1) 是一种中枢晚期促炎细胞因子，可在脓毒症期间触发炎症反应。然而，HMGB1是否参与脓毒症脑损伤的发病机制尚不清楚。在这项研究中，我们研究了 HMGB1 在调节脓毒症大鼠模型脑损伤中的作用。对 Wistar 大鼠进行盲肠结扎和穿刺（CLP）以诱导脓毒性脑损伤。苏木精和伊红染色用于检测皮质的病理变化。使用免疫染色确定 HMGB1 的细胞定位。通过蛋白质印迹检测 HMGB1（其晚期糖基化终产物 (RAGE) 的受体）和下游效应器核因子 kappa-B (NF-κB) 亚基 p65 的皮质水平。HMGB1 通过从细胞核易位（主要在神经元中）在细胞质中增加。此外，脓毒性脑损伤后 RAGE 和 NF-κB p65 上调。丙酮酸乙酯是 HMGB1 的抑制剂，通过抑制细胞质中 HMGB1 的表达，下调 RAGE 和 NF-κB p65 的表达。总的来说，我们的研究结果表明 HMGB1 及其信号转导在脓毒症脑损伤的发病机制中具有关键作用。 HMGB1 抑制可能是脓毒性脑损伤的潜在新治疗靶点。
High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining. Cortical levels of HMGB1, its receptor for advanced glycation end-products (RAGE), and downstream effecter, nuclear factor kappa-B (NF-κB) subunit p65, were detected via western blot.HMGB1was increased in the cytoplasm via translocation from the nucleus predominantly in neurons. Moreover, RAGE and NF-κB p65 were upregulated after septic brain injury. Ethyl pyruvate, an inhibitor of HMGB1, down-regulated the expression of RAGE and NF-κB p65via inhibiting HMGB1 expression in the cytoplasm. Collectively, our findings suggest that HMGB1 and its signaling transduction have critical roles in the pathogenesis of septic brain injury. HMGB1 inhibition might be a potential new therapeutic target for septic brain injury.