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

ABSTRACT

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.

Keywords::

• liver transplantation
• ischemia reperfusion injury
• LXRs
• TLR4
• NF-κB

View retraction statement:

Statement of Retraction: Liver X Receptors Activation Attenuates Ischemia Reperfusion Injury of Liver Graft in Rats

DECLARATION OF INTERESTS

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

FUNDING

This research was supported by the National Natural Science Foundation of China (grant number 81671580) and the Natural Science Foundation of Chongqing (grant number csct2017jcyjAX0440).