Liver X Receptors Activation Attenuates Ischemia Reperfusion Injury of Liver Graft in Rats.

PURPOSE: Suppression of the Toll like receptor 4 (TLR4)-nuclear factor-κB (NF-κB) signaling was critical in protection against liver IRI. Previous studies revealed that Liver X receptors (LXRs) activation could antagonize TLR4-NF-κB signaling. The purpose of this study is to determine whether LXRs agonist GW3965 can suppress the TLR4-NF-κB signaling during liver transplantation and protect ischemia-reperfusion injury (IRI).

MATERIALS AND METHODS: Sprague Dawley (SD) rats were used to perform orthotropic liver transplantation. Donors were pretreatment with GW3965 (0.3 mg/kg) through caudal vein injection 30 min before the surgery. The followings were analyzed after transplantation: alanine aminotransferase (ALT), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) level in serum, ATP binding cassette transporter A1 (Abca1) expression, NF-κB transcriptional activity, apoptosis and histological injury.

RESULTS: GW3965 pretreatment significantly ameliorated the degree of IRI associated with the effects of upregulating Abca1 expression, inhibiting NF-κB transcriptional activity, and downregulating TNF-α and IL-6 level.

CONCLUSION: LXRs activation attenuated hepatic IRI by preventing TLR4-NF-κB signaling.