大剂量抗凝血酶 III 通过减轻大鼠全身炎症反应预防热射病。
High-dose antithrombin III prevents heat stroke by attenuating systemic inflammation in rats.
机构信息
Department of Anesthesiology and Intensive Care Medicine, Oita University, Yufu City, Japan.
出版信息
Inflamm Res. 2010 Jul;59(7):511-8. doi: 10.1007/s00011-009-0155-y. Epub 2010 Jan 3.
OBJECTIVE
Systemic inflammatory mediators, including the high mobility group box 1 (HMGB1) protein, play important roles in the development of various inflammatory conditions. Although anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, their anti-inflammatory mechanism of action is not well understood. Nevertheless, as heat stroke is a severe inflammatory response disease, we hypothesized that AT III would inhibit inflammation and prevent heat stress-induced acute heat stroke.
METHODS
Male Wistar rats received a bolus injection of saline or 250 U of AT III per kg of body weight into the tail vein, followed by heat stress (exposure to 42 degrees C for 30 min). Levels of cytokines (interleukin-1 beta, interleukin-6, and TNF-alpha), NOx, and HMGB1 were measured in serum and tissue at regular intervals for 6 h after the heat stress induction.
RESULTS
Levels of cytokines, NOx, and HMGB1 in serum decreased over time in AT III-treated rats. AT III pretreatment also reduced NOx levels during heat stress-induced inflammation. As a result, AT III pretreatment improved survival in a rat model of heat stress-induced acute inflammation.
CONCLUSIONS
Our data suggest that AT III pretreatment inhibited the secretion of cytokines, NOx, and HMGB1, and prevented heat stress-induced acute inflammation.
目的
全身性炎症介质，包括高迁移率族蛋白 B1（HMGB1），在各种炎症状态的发展中发挥重要作用。尽管抗凝剂，如抗凝血酶 III（AT III），可抑制各种原因引起的炎症，但它们的抗炎作用机制尚不清楚。然而，由于中暑是一种严重的炎症反应性疾病，我们假设 AT III 将抑制炎症并预防热应激引起的急性中暑。
方法
雄性 Wistar 大鼠尾静脉注射盐水或 250 U/kg 体重的 AT III，然后进行热应激（42°C 暴露 30 分钟）。在热应激诱导后 6 小时内定期测量血清和组织中的细胞因子（白细胞介素-1β、白细胞介素-6 和 TNF-α）、NOx 和 HMGB1 水平。
结果
AT III 治疗组的血清细胞因子、NOx 和 HMGB1 水平随时间推移而降低。AT III 预处理还降低了热应激诱导炎症期间的 NOx 水平。因此，AT III 预处理改善了热应激诱导的急性炎症大鼠模型的存活率。
结论
我们的数据表明，AT III 预处理抑制了细胞因子、NOx 和 HMGB1 的分泌，并预防了热应激引起的急性炎症。
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