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

DOI: 10.12201/bmr.202410.00066

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  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

  Submit time: 28 October 2024

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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