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Insulin in Uw Solution Exacerbates the Ischemia/Reperfusion Injury in Rat Liver Transplantation: (English)

Insulin in Uw Solution Exacerbates the Ischemia/Reperfusion Injury in Rat Liver Transplantation: (English)

          
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This dissertation, "Insulin in UW solution exacerbates the ischemia/reperfusion injury in rat liver transplantation" by Xianliang, Li, 李先亮, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled INSULIN IN UW SOLUTION EXACERBATES THE ISCHEMIA/REPERFUSION INJURY IN RAT LIVER TRANSPLANTATION Submitted by Li Xian-Liang for the degree of Doctor of Philosophy at The University of Hong Kong in August, 2003 Background: University of Wisconsin (UW) solution has been a preferred storage solution in liver transplantation. However, extended cold preservation with UW solution is highly related to primary graft nonfunction, biliary stricture, and poor patient survival rate. Insulin is known to promote anabolism and is added to UW solution. While organ preservation aims to decrease the metabolic rate, the value of insulin and the metabolism of the liver graft in UW solution remain unclear and deserve further study. Objectives: This study aims to (1) determine the effects of insulin currently used in UW solution on ischemia/reperfusion (I/R) injury; (2) clarify the mechanism of cell apoptosis during preservation; (3) investigate the regulation of energy metabolism and related genes by insulin during preservation; (4) study the regulation of phosphatidylinositol 3-kinase (PI3-Kinase)/Akt pathway by insulin during preservation. Methods and results: Liver grafts harvested from Lewis rats were used as donors and preserved by UW solution with (UWI group) or without insulin (UW group) for 0, 3, 7, 9, and 24 hours. The liver grafts preserved for 7, 9, and 24 hours were implanted to recipients (Lewis rats) using the modified Kamada's technique without hepatic artery reconstruction. The data showed that insulin exacerbated I/R injury by decreasing the graft survival rates, deteriorating graft function, accelerating apoptosis and necrosis, and downregulating the expression of intragraft regeneration-related genes after transplantation, which was obtained by cDNA microarray study. For the preserved grafts, positive apoptotic nuclei stained by TUNEL could be found in hepatocytes at the beginning of preservation and in endothelial cells after 9 hours of preservation in the UWI groups. Upregulation of caspase-12 and activation of caspase-3 and 7 were detected by Western-blot in UWI groups and contributed to cell apoptosis during preservation. Insulin in UW solution decreased adenosine triphosphate (ATP) and energy charge (EC) levels after transplantation, which were derived from high performance liquid chromatography study. Insulin also exacerbated ATP, EC, and total adenine nucleotides depletion by maintaining anabolic activities after 3 hours of preservation. Activation of glucokinase accounted for the maintenance of ATP and EC levels during the first 3 hours of preservation, while upregulation of fatty acid synthase and phospho-glycogen synthase kinase-3β contributed to energy depletion after 3 hours of preservation. Glucose and lipid metabolism processes were regulated by insulin through the insulin receptor substrate-2/sterol regulatory element binding protein-1c pathway at the mRNA level. The PI3-Kinase/Akt pathway was activated by phosphorylation at Thr 308 and Ser 473 during preservation and upregulated by insulin. Caspase-9, one of the targets of PI3-Kinase/Akt pathway, was downregulated by insulin during the preservation. However, higher expression levels of Bad and phospho-glycogen synthase kinase-3β could be detected by Western-blot in the UWI groups and contributed to cell apoptosis. C


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Product Details
  • ISBN-13: 9781374710818
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 152
  • Spine Width: 10 mm
  • Width: 216 mm
  • ISBN-10: 1374710814
  • Publisher Date: 27 Jan 2017
  • Binding: Hardback
  • Language: English
  • Series Title: English
  • Weight: 644 gr


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Insulin in Uw Solution Exacerbates the Ischemia/Reperfusion Injury in Rat Liver Transplantation: (English)
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