Abstract: Objective To investigate whether RNA interference (RNAi) of LXRα gene in donor rats with fatty liver improves
liver graft function after transplantation. Methods Fifty donor SD rats were fed a high-fat diet and 56% alcohol to induce
macrovesicular steatosis exceeding 60% in the liver. The donor rats were injected via the portal veins with 7 × 107 TU
LXRα-RNAi-LV mixture (n=25) or negative control-LV (NC-LV) vector (n=25) 72 h before orthotopic liver transplantation. At 2,
24, and 72 h after the transplantation, the recipient rats were sacrificed to examine liver transaminases, liver graft histology,
immunostaining (TUNEL), and protein and mRNA levels of LXRα. Results Lentivirus-LXRα RNAi inhibited LXRα gene
expression at both the mRNA and protein levels in the liver graft and reduced the expressions of SREBP-1c and CD36 as
compared with the controls, resulting also in reduced fatty acid accumulation in the hepatocytes. The recipient rats receiving
RNAi-treated grafts showed more obvious reduction in serum ALT, AST, IL-1β and TNF-α levels, and exhibited milder hepatic
pathologies than the control rats after the transplantation. TUNEL assay demonstrated a significant reduction in cell apoptosis
in LXRα-RNAi-LV-treated liver grafts, and the rats receiving treated liver grafts had a prolonged mean overall survival time.
Conclusion LXRα-RNAi-LV treatment of the donor rats with fatty liver can significantly down-regulate LXRα gene expression
in the liver graft and improve the graft function and recipient rat survival after liver transplantation.