LXRα gene downregulation by lentiviral-based RNA interference enhances liver function after fatty liver transplantation in rats
Ying-Peng Zhao, Li Li, Jing-Pan Ma, Gang Chen and Jian-Hua Bai
Kunming, China
Author Affiliations: Department of Hepatobiliary and Transplantation Surgery, Ganmei Affiliated Hospital, Kunming Medical University, Kunming 650011, China (Zhao YP, Li L, Ma JP, Chen G and Bai JH)
Corresponding Author: Li Li, PhD, Department of Hepatobiliary and Transplantation Surgery, Ganmei Affiliated Hospital, Kunming Medical University, No. 504, Qingnian Road, Kunming 650011, China (Tel: +86- 871-63188092; Fax: +86-871-63188091; Email: ynkmlili62@hotmail.com)
BACKGROUND: Steatotic liver grafts, although accepted, increase the risk of poor posttransplantation liver function. However, the growing demand for adequate donor organs has led to the increased use of so-called marginal grafts. Liver X receptor alpha (LXRα) is important in fatty acid metabolism and interrelated with the specific ischemia-reperfusion injury in fatty liver transplantation. This study aimed to investigate whether LXRα RNA interference (RNAi) could improve the organ function of liver transplant recipients.
METHODS: Fifty Sprague-Dawley rats were fed with a high-fat diet and 56% alcohol. The livers of these animals had greater than 60% macrovesicular steatosis and were used as liver donors. The experimental donors were treated with 7×107 TU LXRα-RNAi-LV of a mixture injection and control donors with negative control-LV vector injection into the portal vein 72 hours before the operation. The effects of LXRα-RNAi-LV were assessed by serum aminotransferases, histology, immunostaining, and protein levels. The transcription of LXRα mRNA was assessed by reverse transcription-polymerase chain reaction.
RESULTS: Compared with controls, LXRα RNAi inhibited the expression of LXRα at the mRNA (0.53±0.03 vs 0.94±0.02, P<0.05) and protein levels (0.51±0.08 vs 1.09±0.12, P<0.05). LXRα RNAi also decreased the expressions of sterol regulatory element-binding protein 1c (SREBP-1c) and CD36. LXRα RNAi consequently reduced fatty acid accumulation in hepatocytes. Compared with control animals, LXRα RNAi-treated group had lower serum alanine aminotransferase, aspartate aminotransferase, interleukin-1β, and tumor necrosis factor-alpha levels and milder pathologic damages. TUNEL analysis revealed a significant reduction of apoptosis in the livers of rats treated with LXRα-RNAi-LV, and overall survival as determined by the Kaplan-Meier method was improved among rats treated with LXRα-RNAi-LV (P<0.05).
CONCLUSION: LXRα-RNAi-LV treatment significantly downregulated LXRα expression and improve steatotic liver graft function and recipient survival after a fatty liver transplantation in rats.
2015, Vol. 14 
