| 房 槟,曹晓瑞,闫 昭,杜天舒,田小溪.MOTS-c通过TLR4对肠源性脓毒症的作用及其机制[J].,2020,(5):843-847 |
| MOTS-c通过TLR4对肠源性脓毒症的作用及其机制 |
| The Effects of MOTS-c on Gut-origin Sepsis Via TLR4 and Its Mechanism |
| 投稿时间：2019-09-01 修订日期：2019-09-25 |
| DOI：10.13241/j.cnki.pmb.2020.05.009 |
| 中文关键词: TLR4 MOTS-c 脓毒症 炎症 |
| 英文关键词: TLR4 MOTS-c Sepsis Inflammation |
| 基金项目:陕西省重点研发计划项目（S2017-ZDYF-YBXM-SF-0353） |
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| 中文摘要: |
| 摘要 目的：脓毒症是机体对感染产生的全身性炎症反应综合征，由于具体机制尚不明确，临床治疗效果不佳，死亡率一直居高不下。本实验通过研究线粒体来源多肽MOTS-c通过影响Toll样受体4在肠源性脓毒症小鼠模型中的作用及其相关机制，寻找新的临床治疗靶标，为感染性疾病的研究开拓新的思路。方法：在盲肠结扎穿孔（CLP）所致肠源性脓毒症小鼠给予MOTS-c处理后检测小肠组织中检测炎症相关因子TNF-α，IL-6，IL-1β水平，检测TLR4表达水平，并且在野生型和TLR4过表达小鼠中构建CLP模型并给予MOTS-c处理，将其与对照组进行比较，以明确TLR4在MOTS-c对脓毒症影响中的作用。结果：在MOTS-c组CLP小鼠模型中，小鼠体内促炎因子TNF-α，IL-6，IL-1β水平与对照组相比显著降低（P＜0.05），此外，TLR4与对照组相比表达下降，进一步在TLR4过表达小鼠CLP模型中对小鼠给予MOTS-c处理发现，MOTS-c对小鼠CLP的抗炎作用被抑制，小鼠体内促炎性因子TNF-α，IL-6，IL-1β水平与野生型小鼠比较均显著上升，差异具有统计学意义，说明过表达TLR4逆转了MOTS-c的抗炎作用，提示MOTS-c可以在肠源性脓毒症中发挥抗炎作用，并且此过程可能依赖于TLR4。结论：MOTS-c可以在脓毒症中抑制小肠上皮细胞中TLR4过度激活，最终抑制炎症，因此可能对脓毒症有治疗效果，有望用于临床治疗。 |
| 英文摘要: |
| ABSTRACT Objective: Sepsis is a systemic inflammatory response syndrome caused by infection. Because the mechanism is still unclear, the clinical treatment effect is not good, and the mortality rate is always high. In this study, the effects of MOTS-c, a mitochondria-derived polypeptide, on toll-like receptor 4 (toll-like receptor 4) in the mouse model of enterogenic sepsis and its related mechanisms were studied to search for new clinical therapeutic targets and to open up new ideas for the research of infectious diseases. Methods: In the enterogenous sepsis in mice caused by cecum ligation perforation (CLP) MOTS-c was given after inspection in the small intestine tissue inflammation. TNF-α, IL-6, IL-1β levels, TLR4 expression level were detected, both in the wild type mice and TLR4 overexpression mice CLP model. The mice were given MOTS-c treatment, then the MOTS-c treated group was compared with the control group as for the pro-inflammatory cytokine level, in order to make clear the role of TLR4 in MOTS-c's effects on sepsis. Results: In the MOTS-c treated CLP group, pro-inflammatory factors TNF-α, IL-6, IL-1β level were significantly decreased compared with the control group (P < 0.05). In addition, TLR4 expression was decreased compared with control group. Furthermore, MOTS-c treatment was given to the TLR4 overexpression CLP mice model and MOTS-c's anti-inflammatory effects on CLP mouse model were suppressed. The pro-inflammatory factors TNF-α, IL-6, IL-1β levels were significantly increased compared with wild type mice which suggested that TLR4 overexpression reverses the anti-inflammatory effects of MOTS-c, showing that MOTS-c play an anti-inflammatory role in enterogenic sepsis, and this process may be dependent on TLR4. Conclusion: MOTS-c can inhibit the excessive activation of TLR4 in intestinal epithelial cells in sepsis, and ultimately inhibit inflammation, so it may have therapeutic effects on sepsis, and is expected to be used in clinical treatment in the future. |
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