The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice
The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice
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DOI：
10.1016/j.intimp.2015.01.011
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发表时间：
2015-03-01
影响因子：
5.6
通讯作者：
Ji, Hui
中科院分区：
文献类型：
--
作者：
Chen, Tong;Mou, Yi;Ji, Hui
CDDO-Me已进入II期临床试验阶段，是一种潜在的治疗癌症和炎症性功能障碍的有效药物，但其对LPS诱导的急性肺损伤（ALI）的治疗效果尚未见报道。本研究的目的是探讨CDDO-Me对脂多糖诱导的小鼠急性肺损伤的保护作用并探讨其可能的机制。BalB/c小鼠在LPS刺激前1小时腹膜内接受CDDO-Me（0.5mg/kg，2 mg/kg）或地塞米松（5 mg/kg），并在6小时后处死。评估W/D比、肺MPO活性、总细胞和中性粒细胞数量、肺组织病理学、BALF中的IL-6、IL-1 β和TNF-α。此外，我们估计了iNOS、IL-6、IL-1 β和TNF-α mRNA的表达和NO的产生以及三种主要的VIAPKs、AkT、I κ B-α和p65的激活。在体内研究中，用CDDO-Me预处理显著改善了W/D比、肺MPO活性、炎性细胞浸润和BALF中炎性细胞因子的产生。此外，CDDO-Me在体外从分子、蛋白质和转录水平上对致病过程的干预具有有益作用。这些分析结果提供了证据表明，CDDO-Me可能是治疗LPS诱导的ALI的潜在治疗候选物。(C)2015 Elsevier B. V.版权所有。
CDDO-Me, initiated in a phase II clinical trial, is a potential useful therapeutic agent for cancer and inflammatory dysfunctions, whereas the therapeutic efficacy of CDDO-Me on LPS-induced acute lung injury (ALI) has not been reported as yet. The purpose of the present study was to explore the protective effect of CDDO-Me on LPS-induced ALI in mice and to investigate its possible mechanism. BalB/c mice received CDDO-Me (0.5 mg/kg, 2 mg/kg) or dexamethasone (5 mg/kg) intraperitoneally 1 h before LPS stimulation and were sacrificed 6 h later. W/D ratio, lung MPO activity, number of total cells and neutrophils, pulmonary histopathology, IL-6, IL-1 beta, and TNF-alpha in the BALF were assessed. Furthermore, we estimated iNOS, IL-6, IL-1 beta, and TNF-alpha mRNA expression and NO production as well as the activation of the three mainlVIAPKs, AkT, I kappa B-alpha and p65. Pretreatment with CDDO-Me significantly ameliorated W/D ratio, lung MPO activity, inflammatory cell infiltration, and inflammatory cytokine production in BALF from the in vivo study. Additionally, CDDO-Me had beneficial effects on the intervention for pathogenesis process at molecular, protein and transcriptional levels in vitro. These analytical results provided evidence that CDDO-Me could be a potential therapeutic candidate for treating LPS-induced ALI. (C) 2015 Elsevier B.V. All rights reserved.