高温中暑（HS）是最致命的疾病。由于HS的病因复杂，临床治疗缺乏有效的药物。赤芍（SK）是紫草的主要活性成分，我们通过体内和体外病理和生化方法评估了其在高温中暑模型（温度：(41 ± 0.5) ℃，相对湿度：(60 ± 5) ％）上的作用。在10mg/kg剂量下，SK延缓了核心体温上升速度，延长了小鼠的存活时间，并显著改善了器官损伤和凝血功能。SK显著降低了血清HS生物标志物白介素-1β（IL-1β）、白介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平，这有助于模型中肝脏和肺脏的保护。通过RNA测序和网络分析，发现有三个通路与IL-17通路存在密切联系。WB和IHC结果表明，SK组中的核因子-κB（NF-κB）p65表达下调（P < 0.05）。核因子样2类似因子2（NFE2L2/Nrf2）和热休克蛋白70（HSP70）的表达上调（P < 0.05）。在HS模型中，附加重组IL-17A蛋白增加了肝脏和肺组织中NF-κB p65的表达水平，附加腹腔注射IL-17A抗体与SK协同抑制组织炎症反应和保护HS效果显著。总之，我们证明SK通过降低IL-17A的产生和抑制其表达，具有在HS模型中发挥抗炎和抗氧化作用的有效化合物。版权所有 © 2023 The Authors. 由Elsevier Masson SAS出版。保留所有权利。

Heat stroke (HS) is the deadliest disease. Due to the complex pathogenesis of HS, lack of effective therapeutic drugs for clinical treatment. Shikonin (SK) is the main active compound of Radix Arnebiae, which was evaluated on the HS model (temperature: (41 ± 0.5) ℃, relative humidity: (60 ± 5) %) via pathological and biochemical approaches in vivo and in vitro. Upon the dose of 10 mg.kg-1, SK delays the rising rate of core temperature, prolongs the survival time of mice, and improves organ injury and coagulation function markedly. Serum HS biomarkers interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were decreased significantly by SK, which contribute to liver and lung protection in the models. Three pathways' responses to heat-stress were found to have a close connection with the IL-17 pathway via RNA sequencing and network analysis. WB and IHC results showed that the nuclear factor-κB (NF-κB) p65 in the SK group was down-regulated (P < 0.05). The expressions of nuclear factor erythroid 2 like 2 (NFE2L2/Nrf2) and heat shock protein 70 (HSP70) were up-regulated (P < 0.05). Additional administration of recombinant IL-17A protein on the HS model up-regulated the expression level of NF- κB p65 in the liver and lung tissue, additional intraperitoneal injection of IL-17A antibody in mice has a synergistic effect with SK in inhibiting tissue inflammatory response and protecting HS. In summary, SK was proved an effective compound for fulfilling the anti-inflammatory and antioxidative capacity of the HS model by reducing the production and inhibiting the expression of IL-17A.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.