Dexmedetomidine ameliorates acute lung injury following orthotopic autologous liver transplantation in rats probably by inhibiting Toll-like receptor 4-nuclear factor kappa B signaling

Background: To investigate whether pretreatment with dexmedetomidine (Dex) has a protective effect against acute lung injury (ALI) in an orthotopic autologous liver transplantation (OALT) rat model and to explore the mechanisms responsible for the protective effect of Dex against lung injury. Methods: Forty-eight rats underwent OALT and were randomly divided into six groups (n = 8 in each group) that received 10 mu g/kg Dex, 50 mu g/kg Dex, 50 mu g/kg Dex + nonspecific alpha(2)-adrenergic receptor (AR) antagonist atipamezole, 50 mu g/kg Dex + specific alpha(2B/C)-AR antagonist ARC-239, 50 mu g/kg Dex + specific alpha(2A)-AR antagonist BRL-44408, or the same amount of normal saline. The sham rats (n = 8) underwent anesthesia induction, laparotomy, and separation of the portal vein without liver ischemia and reperfusion. Lung tissue sections were stained with hematoxylin and eosin (HE) to visualize the damage. The expression of Toll-like receptor 4 (TLR4) and the phospho-nuclear factor (NF)-kappa B p65 subunit as well as inflammatory cytokines was measured. Results: Rats exhibited increased histological lung injury scores and pulmonary edema following OALT. Pretreatment with 50 mu g/kg Dex attenuated OALT-induced lung injury in rats, probably by inhibiting the activation of the TLR4-NF-kappa B signaling pathway. The protective effect of Dex could be blocked by atipamezole or BRL-44408, but not by ARC-239, suggesting these effects of Dex were mediated, at least in part, by the alpha(2A)- AR. Conclusions: Dex exerts protective effects against ALI following OALT, and this protection is associated with the suppression of TLR4-NF-kappa B signaling. Thus, pretreatment with Dex may be a useful method for reducing lung damage caused by liver transplantation.