Ubiquitin reduces fluid shifts after traumatic brain injury
Ubiquitin reduces fluid shifts after traumatic brain injury
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DOI：
10.1016/j.surg.2005.06.026
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发表时间：
2005-09-01
期刊：
影响因子：
3.8
通讯作者：
Majetschak, M
中科院分区：
文献类型：
--
作者：
Earle, SA;Proctor, KG;Majetschak, M
背景Ubiquitin有很好的描述。细胞内特性最近的数据还表明，细胞外泛素的多效性作用，包括诱导细胞凋亡，调节免疫功能，并在严重创伤液体复苏的治疗潜力。然而，外源性泛素在创伤性脑损伤（TBI）后的作用尚不清楚。系列1：TBI和出血后35分钟，静脉注射1.5 mg泛素/kg（n = 5）或白蛋白（n = 5），随后进行液体复苏，以维持平均动脉和脑灌注压。系列2：仅在TBI后施用泛素（n = 5）或媒介物（n = 6）。应用酶联免疫吸附法测定血清、尿液（系列1）和脑脊液（系列2）中的泛素，测定时间为300 min。系列1：静脉推注后，血清泛素在t = 45分钟达到峰值，半衰期为54分钟。尿液回收率为10%。白蛋白与泛素相比，需要多85%的复苏液来稳定全身和脑血流动力学（t = 150至300分钟，P <0.05），但红细胞压积相似。使用白蛋白时，颅内压、吸气峰压进行性升高，氧合降低。所有这些都被泛素显著减弱（所有P <0.05 vs白蛋白）。系列二：静脉注射泛素改变了脑脊液泛素，增加了达峰时间（t = 88 +/- 13 min vs 45 +/-7 min，P <0.05）和浓度-时间曲线下面积（82 +/- 22 vs 23 +/- 11 pg/min（1）/mL（-1），P <0.05）。在TBI后，静脉内泛素穿过血脑屏障，并在复苏期间显著减少了液体进入脑和肺的第三间隔。
Background. Ubiquitin has well-described. intracellular properties. Recent data also suggest pleiotropic effects of extracellular ubiquitin, including induction of apoptosis, regulation of immune functions, and therapeutic potential during fluid resuscitation from severe trauma. However, the actions of exogenous ubiquitin after traumatic brain injury (TBI) are unknown.Methods. Series 1: Thirty-five minutes after TBI and hemorrhage, 1.5 mg ubiquitin/kg (n = 5) or albumin (n = 5) intravenous was followed by fluid resuscitation to maintain mean arterial and cerebral perfusion pressure. Series 2: Ubiquitin (n = 5) or vehicle (n = 6) was administered ater TBI only. Ubiquitin was measured with enzyme-linked immunosorbent assay in serum, urine (series 1), and cerebrospinal fluid (series 2) for 300 minutes.Results. Series 1: After intravenous bolus, serum ubiquitin peaked at t = 45 minutes with a half-life of 54 minutes. Recovery in urine was 10 %. With albumin versus ubiquitin, 85 % more resuscitation fluid was required to stabilize systemic and cerebral hemodynamics (P < .05 for t = 150 to 300 minutes), but hematocrit was similar. With albumin there were progressive increases in intracranial pressure, peak inspiratory pressure, and decreases in oxygenation. All were significantly attenuated by ubiquitin (all P < .05 vs albumin). Series 2: Intravenous ubiquitin altered cerebrospinal fluid ubiquitin with an increased time to peak (t = 88 +/- 13 min vs 45 +/- 7min, P < .05) and area under the concentration-tinie curve (82 +/- 22 vs 23 +/- 11 pg/min(1)/mL(-1), P < .05).Conclusions. After TBI, intravenous ubiquitin crossed the blood brain barrier and significantly reduced, third spacing of fluid into the brain and lung during resuscitation.