Lentiviral-mediated RNA interference of LXRαgene in donor rats with fatty liver enhances liver graft function after transplantation
10.3969/j.issn.1673-4254.2014.07.18
- VernacularTitle:重组慢病毒介导LXRαRNA干扰改善大鼠脂肪肝供肝移植术后的功能
- Author:
Yingpeng ZHAO
1
;
Li LI
;
Jingpan MA
;
Gang CHEN
;
Jianhua BAI
Author Information
1. 昆明市第一人民医院暨昆明医科大学附属甘美医院肝胆胰外科
- Keywords:
fatty liver;
liver transplantation;
LXRα;
RNA interference;
ischemia-reperfusion injury
- From:
Journal of Southern Medical University
2014;(7):1005-1010
- CountryChina
- Language:Chinese
-
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.
