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Biomed Pharmacother. 2018 Oct;106:210-216. doi: 10.1016/j.biopha.2018.06.059. Epub 2018 Jun 28.

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

Author information

1
Department of Critical Care Medicine, The First A ffiliated Hospital of Harbin Medical University, China.
2
Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, China.
3
Department of Critical Care Medicine, The Cancer Hospital of Harbin Medical University, China.
4
Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, China. Electronic address: wanghongliang29@126.com.
5
Department of Critical Care Medicine, The Cancer Hospital of Harbin Medical University, China; Institute of Critical Care Medicine in Sino Russian Medical Research Center of Harbin Medical University, China. Electronic address: drkaijiang1@126.com.

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.

KEYWORDS:

Acute kidney injury; Apoptosis; Dexmedetomidine; Inflammation; Lipopolysaccharide; Sepsis

PMID:
29960167
DOI:
10.1016/j.biopha.2018.06.059
[Indexed for MEDLINE]

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