Roth G A, Moser B, Krenn C, Roth-Walter F, Hetz H, Richter S, Brunner M, Jensen-Jarolim E, Wolner E, Hoetzenecker K, Boltz-Nitulescu G, Ankersmit H J
Department of Surgery, Vienna Medical School, Vienna, Austria.
Eur J Clin Invest. 2005 Jun;35(6):399-403. doi: 10.1111/j.1365-2362.2005.01508.x.
Recently, circulating proteasome core particles (20S proteasome) have been suggested as a marker of cell damage and immunological activity in autoimmune diseases. Aberrant leucocyte activation and increased lymphocyte apoptosis with consecutive T-cell unresponsiveness is deemed to play a pivotal role in the sepsis syndrome. Moreover sepsis-induced muscle proteolysis mainly reflects ubiqutin proteasome-dependent protein degradation. We therefore sought to investigate serum levels of 20S proteasome in critical ill patients.
Case-control-study at a university hospital intensive care unit; 15 patients recruited within 24-48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h of admission to the ICU, a control group of 15 patients who underwent abdominal surgery, and 15 healthy volunteers. ELISA was used to measure the concentration of 20S proteasome in the sera of the patients and controls. Data are given as mean +/- SEM. Mann-Whitney U-test was used to calculate significance and a P-value of 0.05 was considered to be statistically significant.
Marked increase of 20S proteasome was detected in the sera of septic patients (33 551 +/- 10 034 ng mL-1) as well as in trauma patients (29 669 +/- 5750 ng mL-1). In contrast, significantly lower concentrations were found in the abdominal surgery group (4661 +/- 1767 ng mL-1) and in the healthy control population (2157 +/- 273 ng mL-1).
Detection of 20S proteasome may represent a novel marker of immunological activity and muscle degradation in sepsis and trauma patients, and may be useful in monitoring the clinical effect of proteasome-inhibitors.
最近，循环中的蛋白酶体核心颗粒（20S蛋白酶体）被认为是自身免疫性疾病中细胞损伤和免疫活性的标志物。异常的白细胞激活以及淋巴细胞凋亡增加并伴有连续的T细胞无反应性被认为在脓毒症综合征中起关键作用。此外，脓毒症诱导的肌肉蛋白水解主要反映了泛素蛋白酶体依赖性蛋白降解。因此，我们试图研究危重症患者血清中20S蛋白酶体的水平。
在一所大学医院的重症监护病房进行病例对照研究；15例脓毒症诊断后24 - 48小时内招募的患者，13例入住重症监护病房24小时内招募的创伤患者，15例接受腹部手术的患者组成的对照组，以及15名健康志愿者。采用酶联免疫吸附测定法（ELISA）测量患者和对照组血清中20S蛋白酶体的浓度。数据以平均值±标准误表示。采用曼-惠特尼U检验计算显著性，P值<0.05被认为具有统计学意义。
脓毒症患者血清中检测到20S蛋白酶体显著增加（33551±10034 ng/mL），创伤患者血清中也显著增加（29669±5750 ng/mL）。相比之下，腹部手术组（4661±1767 ng/mL）和健康对照组人群（2157±273 ng/mL）的浓度明显较低。
检测20S蛋白酶体可能代表脓毒症和创伤患者免疫活性及肌肉降解的一种新标志物，并且可能有助于监测蛋白酶体抑制剂的临床效果。
