Department of Anesthesiology and Perioperative Medicine, Kanazawa Medical University, Daigaku 1-1, Uchinada, Ishikawa, 920-0293, Japan,
J Anesth. 2013 Oct;27(5):684-92. doi: 10.1007/s00540-013-1584-x. Epub 2013 Mar 27.
High mobility group box 1 (HMGB1), a ubiquitous nuclear protein, induces several inflammatory diseases and functions as a fatal factor when released extracellularly. The effect of HMGB1 on vascular reactivity during sepsis remains to be clarified.
A rat model of abdominal sepsis was produced by cecal ligation and puncture (CLP) under sevoflurane anesthesia (n = 28). Anti-HMGB1 antibody at a dose of 4 or 0.4 mg/kg, or normal saline was injected twice intravenously, i.e., immediately after the CLP surgery and 4 h thereafter. Rats in the sham group underwent laparotomy, and the cecum was manipulated but not ligated or punctured. The descending thoracic aorta was excised 12 h after the CLP surgery and cut into rings of approximately 3 mm in length. Changes in the expression of HMGB1 and vascular reactivity were examined in the rings shortly after harvest and 4 h thereafter.
HMGB1 was identified immunohistochemically and by Western blotting in the nuclei of vascular endothelial and smooth muscle cells in all groups shortly after excision of the aorta, but its expression was augmented only in the CLP groups 4 h thereafter. Degenerated smooth muscle cells were also observed after CLP. Anti-HMGB1 antibody dose-dependently inhibited the augmentation of HMGB1 expression and the morphological changes induced by CLP. The expression of HMGB1 partly correlated with suppression of vascular reactivity.
The present results strongly suggest that HMGB1 plays an important role in vascular malfunction from an early phase of sepsis.
高迁移率族蛋白 B1（HMGB1）是一种普遍存在的核蛋白，当它从细胞外释放时，会引发多种炎症性疾病，并成为致命因素。HMGB1 在脓毒症期间对血管反应性的影响仍有待阐明。
在七氟醚麻醉下（n = 28）通过盲肠结扎和穿刺（CLP）建立大鼠腹腔脓毒症模型。以 4 或 0.4 mg/kg 的剂量静脉注射两次抗 HMGB1 抗体，即 CLP 手术后立即和 4 小时后。假手术组大鼠行剖腹术，仅操作盲肠但不结扎或穿刺。CLP 手术后 12 小时切除降胸主动脉，并切成约 3mm 长的环。在采集后不久和 4 小时后检查环中 HMGB1 的表达变化和血管反应性。
HMGB1 在所有组的主动脉切除后不久，通过免疫组织化学和 Western blot 在血管内皮和平滑肌细胞的核中被识别，但仅在 CLP 组 4 小时后其表达增加。CLP 后还观察到平滑肌细胞变性。抗 HMGB1 抗体剂量依赖性地抑制 CLP 诱导的 HMGB1 表达增加和形态变化。HMGB1 的表达与血管反应性的抑制部分相关。
这些结果强烈表明，HMGB1 在脓毒症早期的血管功能障碍中起重要作用。
