Lentiviral-mediated RNA interference of LXRα gene in donor rats with fatty liver enhances liver graft function after transplantation / 南方医科大学学报
Journal of Southern Medical University
; (12): 1005-1010, 2014.
Article
em Zh
| WPRIM
| ID: wpr-312649
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate whether RNA interference (RNAi) of LXRα gene in donor rats with fatty liver improves liver graft function after transplantation.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
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Índice:
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Assunto principal:
Fisiologia
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Cirurgia Geral
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RNA Mensageiro
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Regulação da Expressão Gênica
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Transplante de Fígado
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Ratos Sprague-Dawley
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Lentivirus
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Hepatócitos
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Biologia Celular
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Interferência de RNA
Limite:
Animals
Idioma:
Zh
Revista:
Journal of Southern Medical University
Ano de publicação:
2014
Tipo de documento:
Article