Objective: To investigate the effect and mechanism of LXRα RNA interference (RNAi) on improving liver function in fatty liver donor rats after liver transplantation.
Method: 50 SD rats were fed a high-fat diet and 56% alcohol to induce fatty liver, as a liver transplant donor, resulting in a fat change of more than 60%. 25 fatty liver donor rats in the experimental group were injected with 7x107 TULXRα-RNAi lentiviral suspension (LXRα-RNAi-LV) from the portal vein 72 hours before transplantation. Twenty-five fatty liver donor rats were injected 72 hours before transplantation as a control group. A negative control lentivirus (NC-LV) carrier fluid was injected into the portal vein. All recipient rats received orthotopic liver transplantation. The levels of liver enzymes, tissue sections, TUNEL, cytokines, tissue proteins and RT-PCR were detected after operation.
Result: Compared with the control group, the LXRα-RNAi-LV treatment group significantly inhibited the accumulation of fatty acids in the transplanted liver cells and the levels of liver enzymes and cytokines related to liver tissue damage. The average survival rate of mice increased, indicating that tissue damage was significantly reduced and slightly increased. T-PCR showed that the level of LXRαmRNA in the experimental group was significantly lower than that of the control group; Western blotting showed that the expression of LXRα, SREBP-1c and CD36 were significantly lower than that of the control group.
Conclusion: LXRα-RNAi-LV gene therapy can significantly reduce the expression of LXRα gene after liver transplantation in fatty liver donor rats, improve liver function, and increase survival rate.