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| 线粒体来源肽MOTS-c在两种脓毒症模型中的保护作用研究 |
| Protective effects of a mitochondrial-derived peptide MOTS-c in two models of sepsis |
| 投稿时间：2019-01-16 修订日期：2019-01-16 |
| DOI： |
| 中文关键词: 线粒体来源肽 MOTS-c 脓毒症 |
| 英文关键词: Mitochondrial-derived peptide MOTS-c Sepsis |
| 基金项目: |
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| 中文摘要: |
| 目的：研究一种新的线粒体来源肽MOTS-c对脓毒症小鼠的保护作用。方法：构建了LPS和CLP诱导的两种脓毒症小鼠模型,观察MOTS-c治疗对小鼠生存率及促炎性因子TNF-α和IL-6水平的影响。Western-blot方法检测MOTS-c对巨噬细胞NF-κB活化的影响。结果: 与对照组相比,MOTS-c治疗使LPS诱导的脓毒症小鼠生存率从10%提高至60% (P < 0.05),而CLP诱导的脓毒症小鼠生存率则从10%提高至50% (P < 0.05)。ELISA结果显示,在LPS诱导的脓毒症模型中,MOTS-c治疗使小鼠血浆中的TNF-α和IL-6的水平显著降低(P < 0.05)；与之类似,在CLP诱导的脓毒症模型中,小鼠血浆和腹腔灌洗液中的TNF-α和IL-6的水平也显著下降(P < 0.05)。机制研究结果表明,MOTS-c能够显著抑制巨噬细胞中LPS诱导的转录因子NF-κB的活化。结论：MOTS-c对脓毒症小鼠具有保护作用,其机制可能与抑制NF-κB的转录激活、降低体内促炎性细胞因子的水平相关。 |
| 英文摘要: |
| Objective: This study aimed to explore the protective effects of a mitochondrial-derived peptide MOTS-c in two in two models of sepsis. Method(s): Two models of sepsis were constructed, one due to lipopolysaccharide (LPS) and the other to cecal ligation and puncture (CLP). The survival rate and pro-inflammatory cytokine levels were detected and compared in septic mice. The influence of MOTS-c on LPS-induced NF-κB activation in macrophages was also analyzed by western-blot. Result(s): Compared to control group, MOTS-c treatment increased the mice survival rate from 10% to 60% in LPS-induced model （P < 0.05）, and from 10% to 50% in CLP-induced sepsis （P < 0.05）separately. The levels of TNF-α and IL-6 in mice blood plasm were decreased in both two septic models by ELISA analysis. Moreover, MOTS-c treatment reduced the TNF-α and IL-6 concentration in peritoneal fluid of CLP-induced septic mice （P < 0.05）. Mechanically, the NF-κB activation was suppressed by MOTS-c in LPS challenged macrophages. Conclusion(s): Our data indicated that MOTS-c could inhibit the activation of NF-κB and suppress the expression of pro-inflammatory cytokines, thus leading to protecting mice from sepsis. |
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