Dexmedetomidine promotes liver regeneration in mice after 70% partial hepatectomy by suppressing NLRP3 inflammasome not TLR4/NFκB

Copyright © 2017 Elsevier B.V. All rights reserved..

Inflammasome activation is mediated by NOD-like receptors (NLRs) that play important role in cellular proliferation. NLRP3 senses the widest array of stimuli. But its role in the liver regeneration after partial hepatectomy (PHx) is still unknown. Dexmedetomidine (Dex) has been documented to protect the liver against ischemia-reperfusion injury via the suppression of the TLR4/NF-κB pathway, which is important for NLRP3 inflammasome activation and liver regeneration. We tested whether Dex contributes to liver regeneration, and investigated its consequent effect on inflammasome activation. In vitro, L02 human liver cells were treated with Dex at different concentrations. The 70% PHx was performed in C57 BL/6 mice as PHx group, and sham-operated animals as Sham group, Dex-treated animals were assigned into two groups: Dex+PHx, which received single intraperitoneal injections of Dex (25μg/kg) before PHx 30mins; Dex+PHx+Dex, which received additional Dex (25μg/kg) after PHx for 3days. Dex significantly inhibited the proliferation of Lo2 cells in vitro and decreased the expression of TLR4/NFκB. In vivo, Dex+PHx exhibited promoted effect on liver regeneration and liver function recovery via inhibiting NLRP3 inflammasome activation. Dex+PH+Dex inhibited the liver regeneration, which may be associated with suppressed expression levels of TLR4/NFκB pathway. Though Dex pretreatment contributed to liver regeneration and function recovery via inflammation suppression, excessive inflammation suppression accompanied with TLR4 suppression could be related to the diminished liver regeneration, suggesting that TLR4/NFκB played important role in liver regeneration and Dex+PHx might be a useful therapeutic strategy to promote liver regeneration in clinical.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:54

Enthalten in:

International immunopharmacology - 54(2018) vom: 05. Jan., Seite 46-51

Sprache:

Englisch

Beteiligte Personen:

Lv, Meihong [VerfasserIn]
Zeng, Huizhi [VerfasserIn]
He, Yi [VerfasserIn]
Zhang, Jiashu [VerfasserIn]
Tan, Guang [VerfasserIn]

Links:

Volltext

Themen:

67VB76HONO
Dexmedetomidine
Inflammasomes
Journal Article
Liver regeneration
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 inflammasome
TLR4/NFκB
TLR4 protein, human
Toll-Like Receptor 4

Anmerkungen:

Date Completed 25.07.2018

Date Revised 04.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2017.10.030

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM27767252X