Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan.
Shock. 2010 Oct;34(4):402-6. doi: 10.1097/SHK.0b013e3181d492e4.
Heatstroke, a severe inflammatory response disease, is a medical emergency characterized by high body temperature. The protein C anticoagulant system inhibits inflammation resulting from various causes. Thrombomodulin (TM), a widely expressed glycoprotein originally identified in vascular endothelium, is an important cofactor in the protein C anticoagulant system. We tested the hypothesis that TM could prevent acute inflammation induced by heat stress in a rodent model. Male Wistar rats received a bolus of 1 mg x kg of body weight of TM or saline injected into the tail vein, followed by heat-stress treatment (exposure to 42°C for 30 min). Serum concentrations of cytokines (IL-1β, IL-6, and TNF-α), NO, and high-mobility group box 1 (HMGB1) protein were measured at various time points after treatment. We observed a decrease in the levels of cytokines and HMGB1 protein in sera of TM-treated animals over time. Inhibition of NO overproduction by recombinant TM was observed during heat stress-induced inflammation. Because of the decline in inflammatory marker levels, TM ameliorated injury to various organs in the rat model of heat stress-induced acute inflammation. As TM exhibited a strong anti-inflammatory effect in a rat model of acute inflammation induced by heat stress, TM represents a potential therapeutic for heatstroke prevention or management in patients.
中暑是一种严重的炎症反应性疾病，以高热为特征，是一种医学急症。蛋白 C 抗凝系统抑制各种原因引起的炎症。血栓调节蛋白（TM），最初在血管内皮细胞中发现的一种广泛表达的糖蛋白，是蛋白 C 抗凝系统的重要辅助因子。我们在啮齿动物模型中检验了 TM 是否可以预防热应激引起的急性炎症的假设。雄性 Wistar 大鼠尾静脉注射 1mg x kg 的 TM 或生理盐水，然后进行热应激处理（42°C 暴露 30 分钟）。在治疗后的不同时间点测量血清细胞因子（IL-1β、IL-6 和 TNF-α）、NO 和高迁移率族蛋白 B1（HMGB1）蛋白的浓度。我们观察到 TM 处理动物的血清细胞因子和 HMGB1 蛋白水平随时间的推移而降低。在热应激诱导的炎症中观察到重组 TM 抑制 NO 过度产生。由于炎症标志物水平下降，TM 改善了热应激诱导的急性炎症大鼠模型中各种器官的损伤。由于 TM 在热应激诱导的急性炎症大鼠模型中表现出强烈的抗炎作用，因此 TM 可能成为预防或治疗中暑的潜在治疗方法。
