Dexmedetomidine protects against lipopolysaccharide-induced sepsis-associated acute kidney injury via an α7 nAChR-dependent pathway.

Abstract

Acute kidney injury (AKI) is a clinical syndrome that results in severe tubular damage with high morbidity and mortality. However, there is a lack of effective therapy strategies. Therefore, it is critical to develop effective drugs for AKI. Dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist, has neuroprotective, anti-inflammatory and sympatholytic properties. The present study aimed to investigate the effect DEX on attenuating the inflammatory reaction and apoptosis in the kidney tissues of septic mice and to explore its underlying mechanisms. Sepsis-induced AKI mice models were generated via intraperitoneal injection of lipopolysaccaride (LPS). DEX reduced LPS-induced local inflammation and tubular apoptosis, which was aggravated in the pathogenesis of renal dysfunction. Reverse transcription-quantitative polymerase chain reaction and western blot analysis results revealed that the expression of pro-apoptotic genes and inflammatory factors were markedly reduced by DEX pretreatment. Furthermore, the protective role of DEX was markedly inhibited by the α7 nicotinic acetylcholine receptor (nAChR) antagonist α-bungarotoxin. These findings provided novel evidence for the anti-apoptotic and anti-inflammatory effects of DEX in LPS-induced AKI mice through an α7 nAChR-dependent signaling pathway.

• Authors: Kai Kang, Yang Gao, Si-Cong Wang, Hai-Tao Liu, Wei-Lan Kong, Xing Zhang, Rui Huang, Zhi-Dong Qi, Jun-Bo Zheng, Jing-Dong Qu, Rui-Jin Liu, Yan-Song Liu, Hong-Liang Wang, Kai-Jiang Yu
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 106 Pg. 210-216 (Oct 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29960167 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Apoptosis Regulatory Proteins
• Chrna7 protein, mouse
• Inflammation Mediators
• Lipopolysaccharides
• alpha7 Nicotinic Acetylcholine Receptor
• Dexmedetomidine

Topics

• Acute Kidney Injury (chemically induced, metabolism, pathology, prevention & control)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Cytoprotection
• Dexmedetomidine (pharmacology)
• Disease Models, Animal
• Inflammation Mediators (metabolism)
• Kidney Tubules (drug effects, metabolism, pathology)
• Lipopolysaccharides
• Male
• Mice, Inbred C57BL
• Sepsis (chemically induced, drug therapy, metabolism)
• Signal Transduction (drug effects)
• Time Factors
• alpha7 Nicotinic Acetylcholine Receptor (metabolism)