Anti-inflammatory effects of propofol are mediated by apolipoprotein M in a hepatocyte nuclear factor-1α-dependent manner
Anti-inflammatory effects of propofol are mediated by apolipoprotein M in a hepatocyte nuclear factor-1α-dependent manner
复制标题
丙泊酚的抗炎作用是由载脂蛋白 M 以肝细胞核因子 1α 依赖性方式介导的
DOI：
10.1016/j.abb.2013.03.002
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发表时间：
2013-05-01
影响因子：
3.9
通讯作者：
Wang, Qian
中科院分区：
文献类型：
--
作者：
Ma, Xin;Hu, Yan-Wei;Wang, Qian
丙泊酚（2，6-二异丙基苯酚）可能是日常实践中最广泛使用的静脉内催眠药。然而，其抗炎特性很少被提及。在这项研究中，我们评估了异丙酚在体内和体外对脂多糖（LPS）诱导的炎症的抗炎活性和机制，发现异丙酚显着抑制LPS诱导的促炎细胞因子，包括肿瘤坏死因子（TNF）-α，白细胞介素（IL）-1 β和IL-6的产生，以及诱导型一氧化氮合酶（iNOS）的表达。同时，LPS处理可抑制肝细胞核因子-1 α（HNF-1 α）和载脂蛋白M（APOM）的表达，而异丙酚处理可补偿LPS诱导的HNF-1 α和APOM表达的下调。然而，丙泊酚不能补偿LPS诱导的APOM表达下调与HNF-1 α siRNA的治疗和丙泊酚对LPS诱导的促炎细胞因子的产生的抑制作用显著补偿与APOM siRNA的治疗。这些结果提供了证据，丙泊酚可能首先通过增强HNF-1 α表达上调APOM表达，然后抑制LPS刺激细胞中促炎细胞因子的产生。因此，我们的研究可能有助于了解异丙酚在全身炎症反应综合征患者中的关键作用。(C)2013 Elsevier Inc. All rights reserved.
Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous hypnotic agent in daily practice. However, its anti-inflammatory properties have seldom been addressed. In this study, we evaluated the anti-inflammatory activity and mechanisms of propofol on lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro and found that propofol markedly inhibited LPS-induced production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6, and expression of inducible nitric oxide synthase (iNOS). At the same time, the expression of hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and apolipoprotein M (APOM) was inhibited by treatment with LPS and LPS-induced down-regulation of HNF-1 alpha expression and APOM expression could be compensated by propofol treatment. However, propofol could not compensate LPS-induced down-regulation of APOM expression by treatment with HNF-1 alpha siRNA and the suppressive effect on LPS-induced pro-inflammatory cytokines production by propofol was significantly compensated by treatment with APOM siRNA. These results provide evidence that propofol may first up-regulate APOM expression by enhancing HNF-1 alpha expression and then inhibit pro-inflammatory cytokine production in LPS-stimulated cells. Therefore, our study may be useful in understanding the critical effect of propofol in patients with systemic inflammatory response syndrome. (C) 2013 Elsevier Inc. All rights reserved.