Goldstein Richard S, Gallowitsch-Puerta Margot, Yang Lihong, Rosas-Ballina Mauricio, Huston Jared M, Czura Christopher J, Lee David C, Ward Mae F, Bruchfeld Annette N, Wang Haichao, Lesser Martin L, Church Adam L, Litroff Adam H, Sama Andrew E, Tracey Kevin J
Department of Emergency Medicine, North Shore University Hospital, North Shore-LIJ, Manhasset, NY 11030, USA.
Shock. 2006 Jun;25(6):571-4. doi: 10.1097/01.shk.0000209540.99176.72.
Cerebral and myocardial ischemia, two of the leading causes of morbidity and mortality worldwide, are associated with inflammation that can lead to multiple organ failure and death. High-mobility group box 1(HMGB1), a recently described mediator of lethal systemic inflammation, has been detected in individuals with severe sepsis and hemorrhagic shock, but its role during ischemic injury in humans is unknown. To determine whether systemic HMGB1 levels are elevated after ischemic injury, a prospective observational study was performed in subjects with a diagnosis of either Acute Coronary Syndrome (ACS) or cerebral vascular ischemia (transient ischemic attack or cerebral vascular accident). Subjects (n, 16; age [mean], 67+/-16.3 years) were enrolled in the North Shore-LIJ emergency department within 24 h of symptom onset. Blood samples were collected, and HMGB1 levels analyzed by Western blot analysis using previously described methods (Wang et al. Science. 1999). Control samples were obtained from healthy age- and sex-matched volunteers (n, 16; age [mean], 68+/-15.8 years). Here, we report that serum HMGB1 levels were significantly elevated in both myocardial ischemia subjects (myocardial control serum HMGB1, 1.94+/-2.05 ng/mL, vs. myocardial ischemia serum HMGB1, 159+/-54.3 ng/mL; P<0.001); and in cerebral ischemia subjects (cerebral control serum HMGB1, 16.8+/-10.9 ng/mL, vs. cerebral ischemia serum HMGB1, 218+/-18.8 ng/mL; P<0.001). These results suggest that systemic HMGB1 levels are elevated in human ischemic disease.
脑缺血和心肌缺血是全球发病和死亡的两大主要原因，与可导致多器官功能衰竭和死亡的炎症相关。高迁移率族蛋白B1（HMGB1）是最近发现的致死性全身炎症介质，在严重脓毒症和失血性休克患者中已检测到，但它在人类缺血性损伤中的作用尚不清楚。为了确定缺血性损伤后全身HMGB1水平是否升高，我们对诊断为急性冠脉综合征（ACS）或脑血管缺血（短暂性脑缺血发作或脑血管意外）的患者进行了一项前瞻性观察研究。研究对象（n = 16；年龄[均值]，67±16.3岁）在症状出现后24小时内进入北岸-长岛犹太医疗中心急诊科。采集血样，采用先前描述的方法（Wang等人，《科学》，1999年）通过蛋白质印迹分析检测HMGB1水平。对照样本取自年龄和性别匹配的健康志愿者（n = 16；年龄[均值]，68±15.8岁）。在此，我们报告，心肌缺血患者（心肌对照血清HMGB1，1.94±2.05 ng/mL， vs. 心肌缺血血清HMGB1，159±54.3 ng/mL；P<0.001）和脑缺血患者（脑对照血清HMGB1，16.8±10.9 ng/mL， vs. 脑缺血血清HMGB1，218±18.8 ng/mL；P<0.001）的血清HMGB1水平均显著升高。这些结果表明，在人类缺血性疾病中全身HMGB1水平升高。
