Int. J. Mol. Sci. 2016, 17(7), 995; 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
Yiheng Wang 1,2,†
, Shan Wu 1,†, Xiaofang Yu 3, Shaoli Zhou 1, Mian Ge 1, Xinjin Chi 1,*
and Jun Cai 1,*
, Shan Wu 1,†, Xiaofang Yu 3, Shaoli Zhou 1, Mian Ge 1, Xinjin Chi 1,*
and Jun Cai 1,*
1
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China
2
Department of Anesthesiology, The First Affiliated Hospital, University of South China, Hengyang 421001, China
3
Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou 350000, China
†
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Johannes Haybaeck
Received: 14 May 2016 / Revised: 14 June 2016 / Accepted: 16 June 2016 / Published: 23 June 2016
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
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. View Full-TextKeywords:
dexmedetomidine; ischemia-reperfusion injury; liver transplantation; TLR4/NF-κB; α2A-adrenoceptor subtype
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Wang, Y.; Wu, S.; Yu, X.; Zhou, S.; Ge, M.; Chi, X.; Cai, J. 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. Int. J. Mol. Sci. 2016, 17, 995.
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