Lentiviral-mediated RNA interference of LXRαgene in donor rats with fatty liver enhances liver graft function after transplantation
ZHAO Yingpeng
LI Li
MA Jingpan
CHEN Gang
BAI Jianhua
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-1βand TNF-αlevels, 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 LXRαgene expression in the liver graft and improve the graft function and recipient rat survival after liver transplantation.
Keywords：fatty liverliver transplantationLXRαRNA interferenceischemia-reperfusion injury
Publication Date：2014-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1005-1010 )