【Animal modeling】-Recombinant lentivirus-mediated LXRα RNA interference improves the function of rat fatty liver donor liver transplantation

  Objective: To investigate the effect and mechanism of LXRα RNA interference (RNAi) in improving liver function in rats with fatty liver after liver transplantation.

  Methods: Fifty SD rats were fed with high-fat diet and 56% alcohol to induce fatty liver with an average degree of steatosis greater than 60% as liver transplant donors. Twenty-five fatty liver donor rats in the experimental group were injected with 7×107 TU LXRα-RNAi lentiviral suspension (LXRα-RNAi-LV) from the portal vein 72 h before transplantation, and 25 fatty liver donor rats in the control group were transplanted The negative control lentivirus (NC-LV) vector solution was injected from the portal vein in the first 72 hours. All recipient rats underwent orthotopic liver transplantation. Postoperative liver enzymes, tissue sections, TUNEL, cytokines, histoprotein and RT-PCR levels were detected.

  Results: Compared with the control group, the LXRα-RNAi-LV treatment group significantly inhibited the accumulation of fatty acids in the hepatocytes of the transplanted liver after the operation, and the levels of liver enzymes and liver tissue damage-related cytokines were significantly decreased, and the tissue damage was milder. Survival rate improved. RT-PCR showed that the mRNA level of LXRα in the experimental group was significantly lower than that in the control group, and Western blotting showed that the expressions of LXRα, SREBP-1c and CD36 were significantly lower than those in the control group.

  Conclusion: LXRα-RNAi-LV gene therapy can significantly reduce the expression of LXRα gene, improve liver function and improve survival rate after liver transplantation in fatty liver donor rats.