Deguchi Takahiro, Tanaka Hiroki, Horioka Kie, Matsuhisa Chihiro, Hayakawa Akira, Takauji Shuhei, Watanabe Shimpei, Goto Masanori, Fujii Yumiko, Takasawa Kumi, Takasawa Akira
Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan.
Sapporo City General Hospital, Sapporo, Hokkaido, Japan.
Med Mol Morphol. 2025 Jul 2. doi: 10.1007/s00795-025-00441-3.
Global warming has increased summer temperatures, leading to a rise in heat stroke-related deaths in Japan. Heat stroke disrupts the body's adaptation to high temperatures, often resulting in severe complications, including liver damage and even death. However, despite the increasing incidence, pathological autopsies remain rare, and the histological changes associated with heat stroke are poorly understood. In this study, we investigated the pathogenesis of heat stroke using a mouse model. Mice were exposed to 45 °C for 30 min and dissected immediately or 24, 48, and 72 h post-exposure. Histological analysis revealed significant lipid accumulation in hepatocytes surrounding the central vein at 24, 48, and 72 h. At 24 h, hepatocytes also exhibited features of early degeneration, including cytoplasmic lysis and chromatin condensation. Lipidomics analysis of liver tissue collected 24 h post-exposure demonstrated a marked increase in 27-hydroxycholesterol levels. These results indicate that heat stress rapidly disrupts hepatic lipid homeostasis, causing cellular damage and metabolic remodeling. The observed lipid accumulation, including elevated 27-hydroxycholesterol, may play dual roles in mediating inflammation and serving as a protective response. Our findings provide new insight into the pathogenesis of heat stroke-induced liver injury and suggest potential molecular targets for early diagnosis and intervention.
全球变暖使夏季气温升高，导致日本与中暑相关的死亡人数增加。中暑会破坏人体对高温的适应能力，常常引发包括肝损伤甚至死亡在内的严重并发症。然而，尽管中暑发病率不断上升，但病理尸检仍然很少见，人们对中暑相关的组织学变化也知之甚少。在本研究中，我们使用小鼠模型研究了中暑的发病机制。将小鼠暴露于45°C环境30分钟，然后立即解剖，或在暴露后24、48和72小时进行解剖。组织学分析显示，在24、48和72小时时，中央静脉周围的肝细胞中有明显的脂质积累。在24小时时，肝细胞还表现出早期变性的特征，包括细胞质溶解和染色质浓缩。对暴露后24小时收集的肝脏组织进行脂质组学分析表明，27-羟基胆固醇水平显著升高。这些结果表明，热应激会迅速破坏肝脏脂质稳态，导致细胞损伤和代谢重塑。观察到的脂质积累，包括27-羟基胆固醇水平升高，可能在介导炎症和作为一种保护反应中发挥双重作用。我们的研究结果为中暑诱导的肝损伤发病机制提供了新的见解，并为早期诊断和干预提出了潜在的分子靶点。
