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The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice

机译：CDDO-ME对小鼠脂多糖诱导的急性肺损伤的保护作用

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摘要

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.
机译：CDDO-ME在II期临床试验中启动，是癌症和炎症功能障碍的潜在有用的治疗剂，而CDDO-ME对LPS诱导的急性肺损伤（ALI）的治疗效果尚未报告。本研究的目的是探讨CDDO-ME对小鼠LPS诱导的Ali的保护作用，并研究其可能的机制。 BALB / C小鼠在LPS刺激之前腹腔内接受CDDO-ME（0.5mg / kg，2mg / kg）或地塞米松（5mg / kg），并在6小时内处死6小时。评估W / D比，肺MPO活性，总细胞和中性粒细胞的数量，BALF中的总细胞和中性粒细胞，肺组织病理学，IL-6，IL-1β和TNF-α。此外，我们估计InOS，IL-6，IL-1β和TNF-αmRNA表达，没有生产以及三个主要碱度值，AKT，I Kappa B-α和P65的活化。使用CDDO-ME的预处理显着改善了VIVO研究中BALF中的W / D比，肺MPO活性，炎症细胞浸润和炎症细胞因子产生。此外，CDDO-ME对体外分子，蛋白质和转录水平的发病机制过程的干预有益的影响。这些分析结果提供了证据表明CDDO-ME可以是治疗LPS诱导的ALI的潜在治疗候选者。 （c）2015 Elsevier B.v.保留所有权利。

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  • 来源
    《International immunopharmacology》 |2015年第1期|共10页
  • 作者

    Chen Tong; Mou Yi; Tan Jiani; Wei Linlin; Qiao Yixue; Wei Tingting; Xiang Pengjun; Peng Sixun; Zhang Yihua; Huang Zhangjian; Ji Hui;

  • 作者单位

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Sch Pharm Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ State Key Lab Nat Med Nanjing 210009 Jiangsu Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

    CDDO-Me; LPS; ALI; RAW 264.7 cells;

    机译：CDDO-ME;LPS;ALI;原始264.7细胞;

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