Apelin attenuates postburn sepsis via a phosphatidylinositol 3-kinase/protein kinase B dependent mechanism: A randomized animal study.

Abstract

INTRODUCTION:

This study aims to investigate whether apelin would regulate inflammatory response and promote survival in an experimental burn sepsis model through a phosphatidylinositol 3-kinase/protein kinase B dependent pathway.

METHODS:

Male BALB/c mice were divided into the following groups: sham, burn, burn sepsis, burn sepsis treated with apelin, burn sepsis treated with apelin plus LY294002, and burn sepsis treated with LY294002 alone. Apelin level and inflammatory cytokines in serum were detected by enzyme-linked immuno sorbent assay. Apelin/APJ (apelin receptor, gene symbol APLNR) mRNA expression in spleen and adhesion molecules levels in lung was detected by real-time polymerase chain reaction. Neutrophil infiltration in lung was determined by myeloperoxidase assay. Phosphorylation of protein kinase B in lung was determined by western blot. Mortality rate was monitored.

RESULTS:

Burn sepsis induced decreased apelin/APJ mRNA expression in spleen and reduced apelin level in plasma, which were both restored by exogenous apelin treatment. Burn sepsis treated with apelin resulted in decreased interleukin-6, tumor-necrosis factor-alpha, interleukin -1β and monocyte chemotactic protein-1 levels in plasma. Mice with apelin treatment also showed decreased neutrophil infiltration and adhesion molecules expression, accompanied by a remarkable increased protein kinase B phosphorylation in lung tissue. The mortality rate in apelin treated animals was also significantly reduced. Importantly, the above effects of apelin were abolished by LY294002 treatment.

CONCLUSION:

Apelin regulates inflammatory response, diminishes inflammatory remote organ damage and improves survival in an experimental model of burn sepsis, which is at least partly mediated by a phosphatidylinositol 3-kinase/protein kinase B dependent pathway.

• Authors: Keqin Luo, Huibao Long, Bincan Xu, Yanling Luo
• Journal: International journal of surgery (London, England) (Int J Surg) Vol. 21 Pg. 22-7 (Sep 2015) ISSN: 1743-9159 [Electronic] England
• PMID: 26163884 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Adipokines
• Apelin
• Apln protein, mouse
• Intercellular Signaling Peptides and Proteins
• RNA, Messenger
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt

Topics

• Adipokines (biosynthesis, genetics)
• Animals
• Apelin
• Blotting, Western
• Burns (complications, genetics, metabolism)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Gene Expression Regulation
• Intercellular Signaling Peptides and Proteins (biosynthesis, genetics)
• Male
• Mice
• Mice, Inbred BALB C
• Phosphatidylinositol 3-Kinase (biosynthesis, genetics)
• Proto-Oncogene Proteins c-akt (biosynthesis, genetics)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Sepsis (etiology, genetics, metabolism)