Li Hongbo, Li Chunhe, Li Jun, Liu Yongrui, Wen Minyong, Wang Lin
Department of Intensive Care Unit, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, People's Republic of China.
Emergency Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, People's Republic of China.
Mol Neurobiol. 2025 Jun 23. doi: 10.1007/s12035-025-05120-z.
Heat stroke (HS) is a life-threatening condition with complex underlying mechanisms, posing challenges for pharmacological treatment. Xuebijing (XBJ) can effectively relieve HS-induced brain injury, but its molecular mechanism is not well-established. This study was conducted to investigate the mechanisms underlying the protective role of XBJ in HS-induced brain injury. HS-induced mice and cell models were established to elucidate the protective effects and underlying mechanisms of XBJ on HS-induced brain injury in vivo and in vitro. HMGB1 knockout (HMGB1) mice and HMGB1 silencing in primary neuronal cells were used to study the effects of XBJ on HMGB1 in HS. Assessments included survival rate, neuronal damage score, and pathological changes. Various techniques such as Western blot, Transmission Electron Microscope (TEM), immunofluorescence staining, RT-qPCR, commercial kits, TUNEL assay, CCK-8, EdU, flow cytometry, and Co-IP assay were employed to assess autophagy, reactive oxygen species (ROS) levels, oxidative stress, inflammation, neuronal apoptosis, and protein complexes. Data revealed that XBJ ameliorated brain damage and neuron apoptosis in HS-exposed mice and promoted autophagy while inhibiting oxidative stress and inflammatory responses, both in vivo and in vitro. Additionally, XBJ alleviated neuronal brain damage, neuron apoptosis, oxidative stress, and inflammatory responses in HS via inducing autophagy. Furthermore, XBJ promoted the cytoplasmic translocation of HMGB1 from the nucleus and competed with Bcl-2 for binding to Beclin1. Moreover, HMGB1 mice and HMGB1 silencing in primary neuronal cells displayed reduced autophagy and enhanced inflammatory responses, both in vivo and in vitro. XBJ protects against HS-induced brain injury via a mechanism involving the autophagy-inflammation pathway mediated by HMGB1.
热射病（HS）是一种具有复杂潜在机制的危及生命的病症，给药物治疗带来了挑战。血必净（XBJ）可有效减轻热射病诱导的脑损伤，但其分子机制尚未完全明确。本研究旨在探讨血必净对热射病诱导的脑损伤发挥保护作用的潜在机制。通过建立热射病诱导的小鼠和细胞模型，以阐明血必净在体内和体外对热射病诱导的脑损伤的保护作用及潜在机制。使用HMGB1基因敲除（HMGB1 -/-）小鼠和原代神经元细胞中HMGB1基因沉默的方法，研究血必净在热射病中对HMGB1的影响。评估指标包括存活率、神经元损伤评分和病理变化。采用多种技术，如蛋白质免疫印迹法、透射电子显微镜（TEM）、免疫荧光染色、RT - qPCR、商业试剂盒、TUNEL检测、CCK - 8、EdU、流式细胞术和免疫共沉淀分析，来评估自噬、活性氧（ROS）水平、氧化应激、炎症、神经元凋亡和蛋白质复合物。数据显示，血必净在体内和体外均能改善热射病小鼠的脑损伤和神经元凋亡，促进自噬，同时抑制氧化应激和炎症反应。此外，血必净通过诱导自噬减轻热射病中的神经元脑损伤、神经元凋亡、氧化应激和炎症反应。进一步研究发现，血必净促进HMGB1从细胞核向细胞质的转位，并与Bcl - 2竞争结合Beclin1。而且，HMGB1 -/-小鼠和原代神经元细胞中HMGB1基因沉默在体内和体外均表现出自噬减少和炎症反应增强。血必净通过涉及由HMGB1介导的自噬 - 炎症途径的机制，对热射病诱导的脑损伤发挥保护作用。
