Lentiviral-mediated RNA interference of LXRα gene in donor rats with fatty liver enhances liver graft function after transplantation.
- Author:
Yingpeng ZHAO
1
;
Li LI
;
Jingpan MA
;
Gang CHEN
;
Jianhua BAI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Fatty Liver; genetics; surgery; Gene Expression Regulation; Hepatocytes; cytology; Lentivirus; Liver; physiology; Liver Transplantation; Liver X Receptors; Orphan Nuclear Receptors; genetics; RNA Interference; RNA, Messenger; Rats; Rats, Sprague-Dawley
- From: Journal of Southern Medical University 2014;34(7):1005-1010
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate whether RNA interference (RNAi) of LXRα gene in donor rats with fatty liver improves liver graft function after transplantation.
METHODSFifty 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.
RESULTSLentivirus-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.
CONCLUSIONLXRα-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.