Effects of exogenous ubiquitin in a polytrauma model with blunt chest trauma.
Effects of exogenous ubiquitin in a polytrauma model with blunt chest trauma.
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DOI：
10.1097/ccm.0b013e3182514ed9
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发表时间：
2012-08
影响因子：
8.8
通讯作者：
Majetschak M
中科院分区：
文献类型：
--
作者：
Baker TA;Romero J;Bach HH 4th;Strom JA;Gamelli RL;Majetschak M
确定CXC趋化因子受体（CXCR）4激动剂泛素治疗是否在由双侧股骨骨折加钝性胸部创伤组成的多发性创伤模型中产生有益作用（损伤严重程度评分18 - 25）。治疗研究。研究实验室。十七头约克郡猪。静脉注射（i.v.）在多发性创伤后60分钟注射1.5 mg/kg泛素或白蛋白（=对照）。麻醉，机械通气的猪进行多发性创伤，然后模拟60分钟的休克阶段。在休克期结束时，给予泛素或白蛋白，并将动物复苏至70 mmHg的平均动脉血压，直至t = 420 min。静脉注射泛素后，泛素血浆浓度在t = 90 min时增加16倍至2870 ± 1015 ng/mL，并随着t1/2 = 60 min而降低。白蛋白组的峰值水平为359 ± 210 ng/mL。两组中同源CXCR4配体基质细胞衍生因子（SDF）-1 α的血浆水平均无变化。泛素治疗降低了动脉乳酸水平，并防止了动脉氧合的持续下降，这发生在白蛋白组复苏期间。与损伤对侧的肺、心脏、脾和空肠的湿重与干重的比率在泛素的作用下较低。用泛素治疗，损伤肺中IL-8、IL-10、TNF α和SDF-1 α的组织水平和对侧肺中IL-8的组织水平分别降低。外源性泛素的管理调节局部炎症反应，改善复苏，减少液体转移到组织和保护动脉氧合后钝性多发伤肺损伤。这项研究进一步支持了泛素是一种有前途的蛋白质治疗剂的观点，并暗示CXCR4是多发性创伤后的药物靶点。
To determine whether treatment with the CXC chemokine receptor (CXCR) 4 agonist ubiquitin results in beneficial effects in a polytrauma model consisting of bilateral femur fractures plus blunt chest trauma (Injury Severity Score 18-25). Treatment study. Research Laboratory. Seventeen Yorkshire pigs. Intravenous (i.v.) injection of 1.5 mg/kg ubiquitin or albumin (=control) at 60 min after polytrauma. Anesthetized, mechanically ventilated pigs underwent polytrauma, followed by a simulated 60 min shock phase. At the end of the shock phase ubiquitin or albumin were administered and animals were resuscitated to a mean arterial blood pressure of 70 mmHg until t = 420 min. After i.v. ubiquitin, ubiquitin plasma concentrations increased sixteen-fold to 2870 ± 1015 ng/mL at t = 90 min and decreased with t1/2 = 60 min. Endogenous plasma ubiquitin increased two-fold in the albumin group with peak levels of 359 ± 210 ng/mL. Plasma levels of the cognate CXCR4 ligand stromal cell-derived factor (SDF)-1α were unchanged in both groups. Ubiquitin treatment reduced arterial lactate levels and prevented a continuous decrease in arterial oxygenation, which occurred in the albumin group during resuscitation. Wet weight to dry weight ratios of the lung contralateral from the injury, heart, spleen and jejunum were lower with ubiquitin. With ubiquitin treatment, tissue levels of IL-8, IL-10, TNFα and SDF-1α were reduced in the injured lung and of IL-8 in the contralateral lung, respectively. Administration of exogenous ubiquitin modulates the local inflammatory response, improves resuscitation, reduces fluid shifts into tissues and preserves arterial oxygenation after blunt polytrauma with lung injury. This study further supports the notion that ubiquitin is a promising protein therapeutic and implies CXCR4 as a drug target after polytrauma.