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- Title
Dexmedetomidine Protects Rat Liver against Ischemia-Reperfusion Injury Partly by the α 2A-Adrenoceptor Subtype and the Mechanism Is Associated with the TLR4/NF-κB Pathway.
- Authors
Yiheng Wang; Shan Wu; Xiaofang Yu; Shaoli Zhou; Mian Ge; Xinjin Chi; Jun Cai
- 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 2-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 2-adrenoceptor antagonists including atipamezole (a nonselective 2 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 2A-adrenoceptor subtype, and the mechanism is due to the suppression of the TLR4/NF-κB pathway.
- Subjects
DEXMEDETOMIDINE; THERAPEUTICS; REPERFUSION injury; ISCHEMIA prevention; ALPHA adrenoceptors; TOLL-like receptors; NF-kappa B
- Publication
International Journal of Molecular Sciences, 2016, Vol 17, Issue 7, p995
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms17070995