Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion.
Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion.
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DOI：
10.1186/cc8152
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Pittet JF
中科院分区：
文献类型：
--
作者：
Cohen MJ;Brohi K;Calfee CS;Rahn P;Chesebro BB;Christiaans SC;Carles M;Howard M;Pittet JF
高迁移率组盒核蛋白1 （HMGB1）是一种DNA核结合蛋白，最近被证明是创伤出血动物模型中无菌炎症的早期触发因素，通过激活toll样受体4 （TLR4）和晚期糖基化终产物受体（RAGE）。然而，HMGB1是否在人类创伤出血后早期释放并与炎症反应和凝血功能障碍的发展有关尚不清楚，因此构成了本研究的目的。168名患者作为一项前瞻性队列研究的一部分，被纳入了一个单一的1级创伤中心的严重创伤患者。在到达急诊室后的10分钟内抽血，然后进行任何液体复苏。采用标准技术测定HMGB1、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、血管性血液病因子（vWF）、血管生成素-2 （Ang-2）、凝血酶原时间（PT）、凝血酶原片段1+2 （PF1+2）、可溶性凝血调节蛋白（sTM）、蛋白C （PC）、纤溶酶原激活物抑制剂-1 （PAI-1）、组织纤溶酶原激活物（tPA）和d -二聚体。基础缺损被用来衡量组织灌注不足。测量结果与从电子病历和创伤登记处获得的结果进行比较。HMGB1血浆水平在人类严重创伤后30分钟内升高，并与损伤严重程度、组织灌注不足、创伤后早期凝血功能障碍和高纤溶以及全身炎症反应和补体激活相关。非幸存者的HMGB1血浆水平明显高于幸存者。最后，后来发生器官损伤（急性肺损伤和急性肾功能衰竭）的患者在创伤后早期也有明显较高的血浆HMGB1水平。这项研究的结果首次证明，HMGB1在人类严重创伤后早期被释放到血液中。HMGB1的释放需要严重的损伤和组织灌注不足，并与创伤后凝血异常、补体激活和严重的全身炎症反应有关。
High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study. One hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry. Plasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma. The results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response.
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HMGB1：内源性危险信号。
影响因子：
5.7
作者：
Klune, John R.;Dhupar, Rajeev;Cardinal, Jon;Billiar, Timothy R.;Tsung, Allan
通讯作者：
Tsung, Allan
DOI：
10.1097/00005373-197403000-00001
发表时间：
1974-01-01
影响因子：
--
作者：
BAKER, SP;ONEILL, B;LONG, WB
通讯作者：
LONG, WB
影响因子：
4.4
作者：
Sama, AE;D'Amore, J;Wang, HC
通讯作者：
Wang, HC
影响因子：
38.9
作者：
Gibot, Sebastien;Massin, Frederic;Bollaert, Pierre-Edouard
通讯作者：
Bollaert, Pierre-Edouard
影响因子：
9
作者：
Ganter, Michael T.;Cohen, Mitchell J.;Pittet, Jean-Francois
通讯作者：
Pittet, Jean-Francois