| Part 1 Expression of Protective Gene A20 and Endothelin-l in Marginal Size Liver GraftsWith innovative surgical techniques and improved immunosuppression, liver transplantation (LTx) continues to be the only definitive mode of therapy for patients with end-stage liver diseases. However, the major factor limiting the application of liver transplantation remains the scarcity of donor organs, which presently accounts for a 10 per cent waiting list mortality rate. Over the last decade, live donor liver transplantation (LDLT), a technical innovation, has developed to offered an expanded donor pool for earlier transplantation, shorter waiting times and excellent quality grafts. The result of LDLT using relatively larger grafts such as right lobe grafts has been satisfactory, with an overall survival rate of 85%. The major concern of adult-to-adult LDLT remains the adequacy of the graft size. The minimum graft size requirement has not yet been precisely known, but studies have indicated that the survival rate of recipients with the GW/ESLV (Graft weight / Estimated standard liver volume) value >40% was higherthan that of recipients with the value <40%. The graft with 40% ratio has been considered as clinically marginal graft with safety limit in some transplantation centers. Both reduced metabolic and synthetic capacity as well as enhanced hepatic injury account for the lower graft and recipient survival. The exact mechanism leading to injury of a small-for-size liver graft after liver transplantation is not yet completely clarified. It has previously been demonstrated that a small-for-size liver graft transplanted into an adult recipient undergoes progressive damage resulted from microcirculatory disturbances due to severe endothelial and hepatocellular injury associated with excessive portal blood flow and transient portal hypertension during early stage of reperfusion.Since discovery of endothelin (ET) in 1988, this peptide has attracted much attention as a strong vasoconstrictive factor hepatic vascular bed. It has been suggested that ET-1 could be involved in microcirculatory regulation through its vasoconstrictor action, as well as in regulating inflammatory response. Recently, it has been demonstrated that A20 gene, as an important protective gene, plays a critical role in inhibiting the expression of NF-icB-dependent proinflammatory genes, such as iNOS, ICAM-1, VCAM-1, E-selectin and IL-8, and then terminating TNF-induced NF-icB responses. Up to now, there is no study about the expression profile of protective gene A20 and ET-1 and its relationship with reperfusion injury in small-for-size liver graft. The aim of this study is to eclucidate the intragraft expression profiles of A20, ET-1 and its relevant genes in liver transplantation using marginal size liver grafts.Materials and methods 1. Animal modelThe rat model of nonarterialized orthotopic liver transplantation using marginal size liver grafts was established in syngeneic (LEW to LEW) rats weighing 220 to 250 g, by the procedure of Kamada and Came. The graft reduction of harvested donor liver was-10-performed ex situ. The marginal size graft was composed of the median lobe by resecting the other lobes. The suprahepatic vena cava was anastomosed end-to-end with a 7-O Prolene running suture. The cuff technique was used for the portal and infrahepatic caval anastomoses. A Teflon tube stent was used for the biliary anastomosis. The survival of animals in Marginal size graft (near 40% of recipient liver weight) group (Ms group) and Whole graft (near 100% of recipient liver weight) group (Ws group) was investigated. Twelve rats in each group were used for study.2. Relevant studiesThe animals in Marginal size graft group (M group) and Whole graft group (W group) were sacrificed at 30 min, 2hr, 6hr, and 24hr after reperfusion, respectively. Blood samples were collected for biochemical measurement. Liver specimens were morphologically examined under light microscopy with Hematoxylin-eosin staining. The mRNA expression of A2...
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