Objective To introduce the mechanisms of graft injuries after small-for-size liver transplantation and protective measures. Methods Recently relevant literatures were reviewed and summarized. Results Portal hypertension after small-for-size liver transplantation induces mechanical injuries as well as hepatic sinusoidal microcirculation disturbance and cytokines release, which worsened the injuries. Decrease portal pressure by surgery or drug could improve grafts function. ConclusionComprehending the mechanisms of graft injuries will contribute a lot for the living donor liver transplantation.
Objective To investigate the effects of adenosine 2A receptor (A2AR) activation on oxidative stress in small-forsize liver transplantation. Methods A rat orthotopic liver transplantation model was performed using 40% graft, 18 recipients were given intravenously saline (control group), CGS21680 (A2AR agonist, CGS21680 group) or ZM241385 (A2AR antagonist, CGS21680+ZM241385 group) randomly. Aspartate aminotransferase (AST), enzymatic antioxidants 〔superoxide dismutase (SOD); catalase (CAT); glutathione peroxidase (GSH-Px)〕, non-enzymatic antioxidants 〔ascorbic acid (AA); glutathione (GSH); α-tocopherol (TOC)〕 and lipid oxidant metabolites malondialdehyde (MDA) were measured and analyzed at 6 h after reperfusion. Results Compared with the control group and CGS21680+ZM241385 group, A2AR activation increased the activities of SOD and GSHPx (Plt;0.05), reduced the productions of AST and MDA (Plt;0.05), increased the levels of AA, GSH and TOC (Plt;0.05) in CGS21680 group. But there was no significant change in CAT activity (Pgt;0.05) among 3 groups. Conclusions A2AR activation improves the antioxidant enzyme activities, promotes the production of antioxidants, and slowes down the increase in MDA level, depresses of the increase in AST activity. A2AR activation suppresses oxidative damage and increases the antioxidant capacity which in turn minimizes their harmful effects of ischemia-reperfusion in small-for-size liver transplantation.
Objective To establish and modify a rat model of arterialized small-for-size orthotopic liver transplantation and investigate the histopathologic changes of the grafts after transplantation. Methods Modified two-cuff technique was applied to establish a rat model of 40% small-for-size orthotopic liver transplantation with a modified microvascular “sleeve” anastomosis between the celiac trunk of donors and the stump of right kidney artery of recipients. Seven days survival rate was observed, main indices of liver function, histopathologic changes of the grafts were detected on the 1st, 2nd, 4th and 7th day after transplantation, respectively. Results The successful rate of operation was 93.3%. Seven days survival rate was 60.0%. The mean time of nonhepatic time was (12.0±2.5) min. Alanine aminotransferase (ALT) and total bilirubin (TB) began to elevate on the first day and peaked on the second day after operation. Histological findings indicated that hepatic sinusoidal and central vein dilation, monocytes infiltration in partial area were found on the 1st day after operation, more diploid and polyploid hepatocytes could be observed on the 4th day after operation. Conclusion The model is easily available and highly reproducible, and the stability of the model is improved by modifying the technique. The histological changes of the grafts are mainly caused by ischemia-reperfusion injury.
Objective To investigate the significance of hepatic arterial reconstruction on the model of 40% small-for-size orthotopic liver transplantation in rats. Methods Modified two-cuff technique was applied to establish a rat model of 40% orthotopic liver transplantation. A total of 240 Sprague Dawley (SD) rats were randomly divided into 2 groups: reconstructive artery group and non-reconstructive artery group. One week survival rate was observed. Main indexes of liver function, histology and the expression of proliferative cell nuclear antigen (PCNA) of liver graft （by immunohistochemical method） were detected on day 1, 2, 4 and 7 after transplantation, respectively. Results One week survival rates of reconstructive artery group and non-reconstructive artery group were 65.0% (13/20) and 50.0% (10/20) respectively (Pgt;0.05). Alanine aminotransferase (ALT) and total bilirubin (TB) began to elevate from day 1 and peaked on day 2 after surgery in two groups. ALT in non-reconstructive artery group on day 2 and 4 were significantly higher than that in reconstructive artery group (P＜0.05). TB in non-reconstructive artery group on day 2 and 7 were significantly higher than that in reconstructive artery group (P＜0.05). Histological findings indicated that more diploid and polyploid hepatocytes and more gently dilation of central veins and hepatic sinusoids could be seen postoperatively in reconstructive artery group. The expression of PCNA of liver graft peaked on day 2 after surgery. The expression of PCNA of reconstructive artery group was higher on day 1 (P＜0.01) and lower on day 7 than that of non-reconstructive artery group after operation (P＜0.05). Conclusions Arterial reconstruction can improve liver function of liver grafts after small-for-size orthotopic liver transplantation, alleviate the histological changes and promote the regeneration of liver grafts quickly.
Objective To examine the effect of zinc finger protein A20 on regeneration of small-for-sized liver allograft, graft rejection and recipient rat survival time. Methods Small-for-sized liver transplantation with 30% partial liver allograft was performed by using a b-rejection combination rat model of DA (RT1a) to Lewis (RT1l) rats. The rats were grouped into rAdEasy-A20 treatment group （A20 group）, the control empty Ad vector rAdEasy treatment group (rAdEasy group) and PS control treatment group (PS group). Ex vivo gene transfer in donor liver graft was performed through portal vein infusion. Animals were assessed for survival days, expression of A20 in liver graft, liver graft regeneration, hepatocyte apoptosis, graft rejection, NF-κB activation and ICAM-1 mRNA expression in liver graft sinusoidal endothelial cells (LSECs), number of liver graft infiltrating mononuclear cells (LIMCs) and the subproportion of NK/NKT cells, and serum IFN-γ level. Results Survival day of A20 group rats was prominently longer than that of PS group rats and rAdEasy group rats (P=0.001 8), whereas survival day of rAdEasy group rats was remarkably shorter than that of PS group rats (P=0.001 8). Regeneration of the small-for-sized liver allograft was markedly augmented by A20, BrdU labelling index of hepatocyte on postoperative day 4 was significantly increased in the A20 group compared with the PS group and rAdEasy group (P＜0.01). Hepatocyte apoptosis on postoperative day 4 was significantly inhibited by A20 (P＜0.01). On postoperative day 4, histologic examination revealed a mild rejection in the A20 group but a more severe rejection in the PS and rAdEasy groups. NF-κB activity and ICAM-1 mRNA expression in LSECs on postoperative day 1 were notably suppressed by A20 overexpression. Flow cytometry analysis showed a marked downregulation of LIMCs number by A20, including more prominent decrease in the subproportion of NK/NKT cells on postoperative day 1 and 4, respectively (P＜0.05). Serum IFN-γ level on postoperative day 4 was also significantly suppressed by A20 overexpression (P＜0.05). Conclusion These data suggest that A20 could effectively promote small-for-sized liver allograft regeneration, suppresses rejection and prolong survival days of recipient rats. These effects of A20 could be related to an inhibition of LSECs activation, suppression of infiltration of LIMCs and the subpopulations such as NK cells and NKT cells into liver graft, and inhibition of hepatocyte apoptosis.