Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan.
J Surg Res. 2011 Dec;171(2):762-8. doi: 10.1016/j.jss.2010.05.008. Epub 2010 Jun 1.
Heat stroke is a condition characterized by high body temperature that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such as danaparoid sodium (DA), inhibit various types of inflammation; however, the anti-inflammatory mechanism of action is not well understood. Given that heat stroke is a severe inflammatory response disease, we hypothesized that DA could inhibit inflammation from heat stress and prevent acute heat stroke.
Male Wistar rats were given a bolus injection of saline or DA (50 U/kg body weight) into the tail vein just prior to heat stress (42 °C for 30 min). Markers of inflammation were then determined in serum and tissue samples.
In rats pretreated with DA, induction of cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α), nitric oxide (NO), and high mobility group box 1 (HMGB1) protein were reduced compared with saline-treated rats. Histologic changes observed in lung, liver, and small intestine tissue samples of saline-treated rats were attenuated in DA-treated rats. Moreover, DA pretreatment improved survival in our rat model of heat stress-induced acute inflammation.
Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke.
热射病是一种以体温升高为特征的病症,可导致多个器官出血和坏死。抗凝剂,如达那肝素钠(DA),可抑制多种类型的炎症;然而,其抗炎作用机制尚不清楚。鉴于热射病是一种严重的炎症反应性疾病,我们假设 DA 可以抑制热应激引起的炎症,预防急性热射病。
雄性 Wistar 大鼠在热应激(42°C 30 分钟)前通过尾静脉给予生理盐水或 DA(50 U/kg 体重)推注。然后测定血清和组织样本中的炎症标志物。
与生理盐水处理的大鼠相比,预先用 DA 处理的大鼠诱导的细胞因子(白细胞介素[IL]-1β、IL-6 和肿瘤坏死因子[TNF]-α)、一氧化氮(NO)和高迁移率族蛋白 1(HMGB1)蛋白减少。在生理盐水处理的大鼠的肺、肝和小肠组织样本中观察到的组织学变化在 DA 处理的大鼠中减弱。此外,DA 预处理提高了我们的热应激诱导急性炎症大鼠模型的存活率。
总之,我们的研究结果表明,DA 预处理可能是热射病的一种新的治疗工具。