Votta-Velis E Gina, Minshall Richard D, Visintine David J, Castellon Maricela, Balyasnikova Irina V
Department of Anesthesiology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
Anesth Analg. 2007 Nov;105(5):1363-70, table of contents. doi: 10.1213/01.ane.0000281144.06703.0d.
Acute lung injury (ALI) is a frequent complication in septic patients. Previously, we found that propofol, a highly lipid-soluble anesthetic, attenuates ischemia-reperfusion and oxidative lung injury in the isolated perfused rat lung. In the present study, we evaluated the effect of propofol on endotoxin-induced ALI and endothelial dysfunction.
The effect of propofol on endotoxin-induced lung endothelial injury was evaluated by plasma and lung tissue homogenate angiotensin I converting enzyme (ACE) activity, pulmonary vascular anti-ACE monoclonal antibody binding, and lung wet weight to body weight ratio (LW/BW).
When injected IV into rats, endotoxin produced endothelial cell injury and lung edema, as indicated by: 1) an increase in plasma ACE activity, 2) a decrease in lung ACE activity and anti-ACE monoclonal antibody binding, and 3) an increase in LW/BW. Monoclonal antibody 1A2 was up to 1.8 times more sensitive than other anti-ACE monoclonal antibodies in detecting the decrease in ACE in lungs of endotoxin-treated rats. Pretreatment of rats with a bolus of propofol before endotoxin injection significantly inhibited the increase in ACE activity in the blood, the decrease in ACE activity in the lung, the decrease in anti-ACE monoclonal antibody binding in the lung, and the increase in LW/BW ratio. Importantly, propofol also significantly increased the survival rate of endotoxin-treated animals. The protective effect of propofol in endotoxin-treated animals in vivo was confirmed in vitro, i.e., propofol decreased endothelial cell injury and ACE shedding from endothelial cells in culture.
These results suggest that propofol offers significant protection against endotoxin-induced pulmonary microvessel endothelial cell injury and that anti-ACE monoclonal antibody 1A2 is a sensitive probe for monitoring endothelial dysfunction and ALI during sepsis.
急性肺损伤（ALI）是脓毒症患者常见的并发症。此前，我们发现丙泊酚，一种高度脂溶性麻醉剂，可减轻离体灌注大鼠肺的缺血再灌注及氧化性肺损伤。在本研究中，我们评估了丙泊酚对内毒素诱导的ALI及内皮功能障碍的影响。
通过血浆和肺组织匀浆血管紧张素I转换酶（ACE）活性、肺血管抗ACE单克隆抗体结合以及肺湿重与体重比（LW/BW）来评估丙泊酚对内毒素诱导的肺内皮损伤的影响。
当静脉注射给大鼠时，内毒素导致内皮细胞损伤和肺水肿，表现为：1）血浆ACE活性增加；2）肺ACE活性及抗ACE单克隆抗体结合减少；3）LW/BW增加。单克隆抗体1A2在检测内毒素处理大鼠肺中ACE减少方面比其他抗ACE单克隆抗体敏感高达1.8倍。在内毒素注射前给大鼠推注丙泊酚预处理可显著抑制血液中ACE活性增加、肺中ACE活性降低、肺中抗ACE单克隆抗体结合减少以及LW/BW比值增加。重要的是，丙泊酚还显著提高了内毒素处理动物的存活率。丙泊酚在体内对内毒素处理动物的保护作用在体外得到证实，即丙泊酚减少了培养内皮细胞的损伤及ACE从内皮细胞的脱落。
这些结果表明丙泊酚对内毒素诱导的肺微血管内皮细胞损伤具有显著保护作用，且抗ACE单克隆抗体1A2是监测脓毒症期间内皮功能障碍和ALI的敏感探针。
