Augmenter of liver regeneration promotes hepatic regeneration depending on the integrity of Kupffer cell in rat small-for-size liver transplantation

Background: Augmenter of liver regeneration (ALR) can promote hepatocyte proliferation and thereby augment liver mass restoration. This study was performed to further explore the mechanism of ALR on liver regeneration in small-for-size liver transplanted rats. Methods: Donor Sprague-Dawley rats were divided into a Kupffer cell (KC)-depleted group (pretreated with GdCl3) and KC-competent group and then further divided into two subgroups: the ALR subgroup (infused with 100 mu g/kg ALR through the portal vein) and non-ALR subgroup. Only the median lobe was retained to establish the small-for-size liver transplantation model. Ten rats from each subgroup were used for the 7 d survival study. In addition, the nuclear factor kappa B activity, reperfusion injury, regeneration of the remnant liver, and tumor necrosis factor alpha and interleukin 6 expression levels were evaluated. Results: ALR could accelerate graft regeneration by increasing nuclear factor kappa B activity to induce tumor necrosis factor alpha and interleukin 6 expression in the KC-competent rats, which resulted in a higher 7 d survival rate. Conclusions: ALR could enhance the hepatocellular proliferation of small-for-size liver grafts, and these effects appeared to deeply depend on the integrity of KCs. (c) 2013 Elsevier Inc. All rights reserved.