Anti-inflammatory and antioxidative effects of propofol on lipopolysaccharide-activated macrophages
Anti-inflammatory and antioxidative effects of propofol on lipopolysaccharide-activated macrophages
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DOI：
10.1196/annals.1338.030
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Wu, CH
中科院分区：
文献类型：
--
作者：
Chen, RM;Chen, TG;Wu, CH
败血症是一种严重且危及生命的综合征，常发生在重症监护室（ICU）患者中。在脓毒症期间，炎性细胞因子和一氧化氮（NO）可过度产生，引起组织和细胞损伤。异丙酚是一种用于ICU患者镇静的静脉药物。我们前期的研究表明异丙酚对巨噬细胞功能有免疫抑制作用。本研究旨在评价丙泊酚对脂多糖（LPS）激活的巨噬细胞中肿瘤坏死因子α（TNF-α）、白细胞介素10（IL-1 β）、IL-6和NO生物合成的抗炎和抗氧化作用。暴露于治疗浓度的丙泊酚（50 μ M），LPS（1 ng/mL），或这两种药物的组合1，6和24小时对巨噬细胞没有细胞毒性。ELISA显示，LPS以时间依赖性方式增加巨噬细胞TNF-α、IL-1 β和IL-6蛋白水平，而丙泊酚显著降低LPS增强的TNF-α、IL-1 β和IL-6蛋白水平。RT-PCR结果显示，LPS诱导TNF-α、IL-1 β和IL-6 mRNA的表达，而异丙酚抑制这些作用。LPS还增加了巨噬细胞NO的产生和诱导型一氧化氮合酶（iNOS）的表达。异丙酚明显抑制LPS诱导的巨噬细胞NO合成。目前的研究表明，异丙酚，在治疗浓度，具有抗炎和抗氧化作用的生物合成TNF-α，IL-1 β，IL-6，和NO在LPS激活的宏细胞和抑制作用在翻译前水平施加。
Sepsis is a serious and life-threatening syndrome that often occurs in intensive care unit (ICU) patients. During sepsis, inflammatory cytokines and nitric oxide (NO) can be overproduced, causing tissue and cell injury. Propofol is an intravenous agent used for sedation of ICU patients. Our previous study showed that propofol has immunosuppressive effects on macrophage functions. This study was designed to evaluate the anti-inflammatory and antioxidative effects of propofol on the biosyntheses of tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL-1 beta), IL-6, and NO in lipopolysaccharide (LPS)-activated macrophages. Exposure to a therapeutic concentration of propofol (50 mu M), LPS (1 ng/mL), or a combination of these two drugs for 1, 6, and 24 h was not cytotoxic to the macrophages. ELISA revealed that LPS increased macrophage TNF-alpha, IL-1 beta, and IL-6 protein levels in a time-dependent manner, whereas propofol significantly reduced the levels of LPS-enhanced TNF-alpha, IL-1 beta, and IL-6 proteins. Data from RT-PCR showed that LPS induced TNF-alpha, IL-1 beta, and IL-6 mRNA, but propofol inhibited these effects. LPS also increased NO production and inducible nitric oxide synthase (iNOS) expression in macrophages. Exposure of macrophages to propofol significantly inhibited the LPS-induced NO biosynthesis. The present study shows that propofol, at a therapeutic concentration, has anti-inflammatory and antioxidative effects on the biosyntheses of TNF-alpha, IL-1 beta, IL-6, and NO in LPS-activated macro-phages and that the suppressive effects are exerted at the pretranslational level.