4.7 Article

Ghrelin upregulates PepT1 activity in the small intestine epithelium of rats with sepsis

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 86, Issue -, Pages 669-676

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2016.12.026

Keywords

Sepsis; Ghrelin; PepT1; Inflammatory response; Cecal ligation and puncture

Funding

  1. Shanghai Municipal Health Bureau [20124307]
  2. Outstanding Young Scienctist Fund of Zhejiang Provincial People's Hospital [zry2015B008]

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Background: Sepsis causes nutritional substrate malabsorption; hence, preventing gut barrier problems and improving the nutritional status in sepsis is a compelling issue. Aims: We tested whether ghrelin administration affects peptide transporter 1 (PepT1) activity in the intestinal epithelium of rats with sepsis. Methods: Sixty male Sprague-Dawley rats were randomly divided into sham-operated, sepsis, and ghrelin-treated groups. The cecum of sham-operated rats was separated after laparotomy without ligation and perforation. Sepsis group rats underwent cecal ligation and puncture (CLP). Mucosal specimens were used for immunohistochemstry, real-time PCR, and western blotting to detect PepT1 distribution, and mRNA and protein expression levels, respectively. TNF-alpha, IL-1 beta, and ghrelin levels were estimated in serum and intestinal mucosal tissue by ELISA. High-performance liquid chromatography was used to measure PepT1 uptake by the epithelial cells. Moreover, survival, body weight, and food intake of the rats were recorded during the 7-day treatment period. Results: All rats in the sham-operated group survived, and 80% of rats in the sepsis group died within 7d of CLP. Treatment with ghrelin attenuated the CLP-induced body weight loss, intestine mucosa damage, and the survival rate was better. In addition, ghrelin attenuated increases in TNF-alpha and IL-1 beta production. The expressions of PepT1 mRNA and protein were higher in ghrelin-treated group rats than in sepsis rats. Moreover, the uptake function of PepT1 was better in ghrelin-treated group rats. Conclusion: Ghrelin treatment can reduce the inflammatory response and greatly upregulate the physiological function of PepT1 in intestinal epithelial cells of rats with sepsis. (C) 2016 Elsevier Masson SAS. All rights reserved.

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