High-dose antithrombin III prevents heat stroke by attenuating systemic inflammation in rats
High-dose antithrombin III prevents heat stroke by attenuating systemic inflammation in rats
复制标题
DOI：
10.1007/s00011-009-0155-y
复制
发表时间：
2010-07-01
影响因子：
6.7
通讯作者：
Noguchi, Takayuki
中科院分区：
文献类型：
--
作者：
Hagiwara, Satoshi;Iwasaka, Hideo;Noguchi, Takayuki
全身炎症介质，包括高迁移率族蛋白1（HMGB 1）蛋白，在各种炎症条件的发展中发挥重要作用。虽然抗凝血剂，如抗凝血酶III（AT III），抑制炎症引起的各种原因，其抗炎作用机制还没有得到很好的理解。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可以抑制炎症并防止热应激诱导的急性中暑。雄性Wistar大鼠接受了盐水或250 U AT III/kg体重的尾静脉推注，然后进行热应激（暴露于42 A摄氏度30分钟）。在热应激诱导后6 h，定期测定血清和组织中细胞因子（白细胞介素-1 β、白细胞介素-6和TNF-α）、NOx和HMGB 1的水平。AT III预处理也降低了热应激诱导的炎症过程中的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。我们的数据表明，AT III预处理抑制了细胞因子、NOx和HMGB 1的分泌，并防止了热应激诱导的急性炎症。
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.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 42A 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.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.Our data suggest that AT III pretreatment inhibited the secretion of cytokines, NOx, and HMGB1, and prevented heat stress-induced acute inflammation.