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PNU-282987 Attenuates Intestinal Epithelial Barrier Dysfunction in LPS-Induced Endotoxemia

  • Ying Zhang
  • Feng Zhou
  • Zhili Wang
  • Zhifeng Li
  • Jianguo LiEmail author
Original Article

Abstract

PNU-282987, the α7 acetylcholine receptor(α7nAchR) agonist, has been repeatedly reported to play a key role in anti-inflammatory action of multiple disease. However, little is known about its effect on LPS-induced intestinal epithelial barrier dysfunction. This study investigated the protective effects and mechanisms of PNU-282987 on intestinal epithelial barrier dysfunction in lipopolysaccharide(LPS)-induced endotoxemic rats. Endotoxemia models were induced by intraperitoneal injection of 10 mg/kg LPS. In the endotoxemic group, results showed increases in ileum mucosal permeability, ultrastructural damage of tight junction and redistribution of zonula occludens-1, apoptosis of intestinal epithelial cells and caspase-3 activation. These changes were significantly improved after PNU-282987 administration(P < 0.05). Pretreatment with α-bungarotoxin before PNU-282987 administration reversed the effects of PNU-282987(P < 0.05). These results indicate that PNU-282987 exerts protective effects on intestinal epithelial barrier dysfunction in LPS-induced endotoxemic rats, and its mechanism may involve the improvement of zonula occludens-1 and inhibition of enterocyte apoptosis in an α7nAchR-dependent manner.

KEY WORDS

PNU-282987 intestinal permeability zonula occludens-1 tight junction apoptosis 

Notes

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China(NO.81560131).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Ying Zhang
    • 1
  • Feng Zhou
    • 2
  • Zhili Wang
    • 1
  • Zhifeng Li
    • 1
  • Jianguo Li
    • 1
    Email author
  1. 1.Department of Critical Care Medicine, Zhongnan HospitalWuhan UniversityWuhanPeople’s Republic of China
  2. 2.Department of Endocrinology, Puren HospitalWuhan University of Science and TechnologyWuhanPeople’s Republic of China

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