UNASSIGNED: Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice.
UNASSIGNED: Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS.
UNASSIGNED: The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.
■健康志愿者的外周血单核细胞(PBMC)转录组测序,经典的中暑患者,和EHS患者。建立EHS小鼠模型,通过H&E染色评价小鼠组织损伤。使用免疫荧光染色观察HMGB1的定位和释放。将人脐静脉内皮细胞(HUVECs)与THP-1细胞共培养,研究HMGB1对巨噬细胞的作用。使用中和性抗HMGB1抗体来评估EHS治疗在小鼠中的功效。
■EHS患者或小鼠的血浆和血清HMGB1水平显著升高。EHS诱导的内皮细胞焦亡促进小鼠HMGB1释放。来自内皮细胞的HMGB1促进巨噬细胞的焦亡,导致EHS条件下的免疫紊乱。施用抗HMGB1显著减轻EHS后的组织损伤和全身炎症反应。
■EHS后,HMGB1从焦化性内皮细胞的释放促进巨噬细胞的焦化性凋亡和全身炎症反应,HMGB1中和抗体治疗EHS具有良好的应用前景。