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Int J Mol Sci. 2016 Jun 23;17(7). pii: E995. doi: 10.3390/ijms17070995.

Dexmedetomidine Protects Rat Liver against Ischemia-Reperfusion Injury Partly by the α2A-Adrenoceptor Subtype and the Mechanism Is Associated with the TLR4/NF-κB Pathway.

Author information

1
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. wyheng1202@126.com.
2
Department of Anesthesiology, The First Affiliated Hospital, University of South China, Hengyang 421001, China. wyheng1202@126.com.
3
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. wsbiosci@sina.com.
4
Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou 350000, China. yxfanesthesia@hotmail.com.
5
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. doctorzsl@sina.com.
6
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. gmsunyatsen@sina.com.
7
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. chixinjin@yeah.net.
8
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. biomedcaijun@hotmail.com.

Abstract

Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling plays a dominant role in the pathogenesis of liver ischemia-reperfusion (IR) injury. Dexmedetomidine (Dex) protects the liver against IR injury via α₂-adrenoceptor activation, but the contribution of TLR4 signaling remains unknown. The authors aimed to examine whether pretreatment with Dex produces hepatic protection and investigate the influence of Dex on TLR4/NF-κB signaling. Dex was given via intraperitoneal injection 30 min prior to orthotopic autologous liver transplantation (OALT) in rats, and three α₂-adrenoceptor antagonists including atipamezole (a nonselective α₂ receptor blocker), ARC-239 (a specific α2B/C blocker) and BRL-44408 (a specific α2A blocker) were injected intraperitoneally 10 min before Dex administration. Histopathologic evaluation of the liver and the measurement of serum alanine aminotransferase activity, TLR4/NF-κB expression in the liver, and pro-inflammatory factors (serum tumor necrosis factor-α, interleukin-1β and hepatic myeloperoxidase) concentrations were performed 8 h after OALT. Dex ameliorated liver injury after OALT probably by suppressing the TLR4/NF-κB pathway and decreasing inflammatory mediator levels. The protective effects of Dex were reversed by atipamezole and BRL-44408, but not by ARC-239, suggesting that these effects were mediated in part by the α2A subtype. In conclusion, Dex attenuates liver injury partly via the α2A-adrenoceptor subtype, and the mechanism is due to the suppression of the TLR4/NF-κB pathway.

KEYWORDS:

TLR4/NF-κB; dexmedetomidine; ischemia-reperfusion injury; liver transplantation; α2A-adrenoceptor subtype

PMID:
27347929
PMCID:
PMC4964371
DOI:
10.3390/ijms17070995
[Indexed for MEDLINE]
Free PMC Article

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