通讯作者: 费丽萍, nmqkl0426@163.com

DOI：10.12201/bmr.202410.00066

Effects of α7 nicotinic acetylcholine receptor agonist on intestinal injury and mitochondrial autophagy in sepsis mice

• 摘要：目的：研究α7烟碱型乙酰胆碱受体（α7nAChR）激动剂PNU-282987对脓毒症小鼠肠损伤及线粒体自噬的影响。方法：雄性C57BL/6J小鼠分为对照组、模型组、PNU-282987组。PNU-282987组在造模前1h和造模后2h分别给予1mg/kg PNU-282987腹腔注射。造模后24h取回肠组织，采用苏木素-伊红染色观察病理改变并进行Chiu’s评分，采用醋酸铀-枸橼酸铅双染色观察线粒体自噬情况，采用western blot实验检测α7nAChR、自噬标志蛋白微管相关蛋白1轻链3（LC3）-Ⅱ/LC3-Ⅰ及Beclin-1、线粒体自噬相关蛋白PTEN诱导激酶 1（PINK1）及Parkin的表达水平；取血清和回肠组织，检测IL-1β、IL-6及IL-10。结果：脓毒症组Beclin-1、LC3-Ⅱ/LC3-Ⅰ的表达水平高于对照组，PNU-282987组Beclin-1、LC3-Ⅱ/LC3-Ⅰ高于脓毒症组（P<0.05）。脓毒症组Chiu’s评分高于对照组，PNU-282987组低于脓毒症组（P<0.05）。脓毒症组α7nAChR水平低于对照组，PNU-282987组高于脓毒症组（P<0.05）。脓毒症组PINK1、Parkin高于对照组，PNU-282987组水平高于高于脓毒症组（P<0.05）。结论：α7nAChR激动剂PNU-282987改善脓毒症小鼠肠损伤，激活回肠组织线粒体自噬、减轻炎症反应是可能的分子机制。

  关键词： 脓毒症；肠损伤；α7烟碱型乙酰胆碱受体；线粒体自噬；炎症反应; ; ; ; 

   

  Abstract: Objective: To investigate the effects of α7 nicotinic acetylcholine receptor(α7nAChR) agonist PNU-282987 on intestinal injury and mitochondrial autophagy in sepsis mice. Methods: Male C57BL/6J mice were divided into control group, model group and PNU-282987 group. In PNU-282987 group, 1mg/kg PNU-282987 was injected intraperitoneally 1 hour before and 2 hours after modeling, respectively. Intestinal tissue was taken back 24 hours after modeling, and pathological changes were observed by hematoxylin-eosin staining and Chius score was made. Mitochondrial autophagy was observed by uranium acetate-lead citrate double staining, and α7nAChR, autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I and Beclin-1, and mitochondrial autophagy-related protein PTEN-induced kinase 1(PINK1) were detected by western blot. Serum and ileum tissues were taken to detect IL-1β, IL-6 and IL-10.Result: The expression levels of Beclin-1, LC3-Ⅱ/LC3-Ⅰ in sepsis group were higher than those in control group, while those in PNU-282987 group were higher than those in sepsis group (P<0.05). Chius score in sepsis group was higher than that in control group, while that in PNU-282987 group was lower than that in sepsis group (P<0.05). The level of α7nAChR in sepsis group was lower than that in control group, while that in PNU-282987 group was higher than that in sepsis group (P<0.05). PINK1 and Parkin in sepsis group were higher than those in control group, and the levels in PNU-282987 group were higher than those in sepsis group (P<0.05).Conclusion: α7nAChR agonist PNU-282987 improves intestinal injury in sepsis mice, the activation of mitochondrial autophagy and reduction of inflammation in ileum may be the related molecular mechanism.

  Key words: Sepsis; Intestinal injury; α7 nicotinic acetylcholine receptor; Mitochondrial autophagy; Inflammation response

  提交时间：2024-10-28

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• 序号	提交日期	编号	操作
  1	2024-09-07	bmr.202410.00066V1	下载

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