Mechanism of Cell Death After Extensive Liver Resection: Apoptosis or Necrosis?

摘要

Introduction: Liver resection of more than 80% induce hepatic failure but the mechanism of the remnant liver dysfunction has not been clarified in detail yet. Apoptosis and necrosis are two different cell death mechanisms. Apoptosis is a fundamental biologic process that is crucial in several physiologic and pathophysiologic processes of the liver. In this study, we analysed mechanism of the liver injury after lethal/extensive hepatectomy in rats.Material and method: Forty Wistar male rats weighing 200 to 250 gm divided into three groups: control group (sham laparatomy, n=10), 70% hepatectomy group (n=15), and 85% hepatectomy group (n=15). All rats underwent relaparotomy 24h later. Liver injury, hepatocyte necrosis and apoptosis were assessed.Results: Liver damage and hepatocyte apoptosis were increased significantly in the 85% hepatectomy groupConclusion: Liver failure after extensive hepatectomy was characterized by increased apoptosis. Introduction Hepatic failure after liver resection in rats increases markedly beyond the classic 2 / 3 resection. Hepatic failure occurs as a result of the remnant liver dysfunction1,2. Liver resection of more than 80% induce hepatic failure, but the mechanism of the remnant liver dysfunction after extensive hepatectomy has not been clarified in detail3.Apoptosis and necrosis are two different cell death mechanisms. Apoptosis, often synonymously used with the term “programmed cell death”, is an active, genetically controlled process that removes unwanted or damaged cells. Apoptosis is a fundamental biologic process that is important in many physiologic and pathophysiologic processes in the liver4,5. For a long time necrosis was considered to be an alternative mechanism to apoptosis. However, recent data indicate that, in contrast to necrosis caused by very extreme conditions. There are many examples when this form of cell death may be a normal physiological and regulated event. Furthermore, signaling pathways, kinase cascades, and mitochondria, participate in both processes and it is possible of these processes to switch to an other6.The aim of this study was to assess mechanism of the liver injury after lethal and nonlethal hepatectomy in rats. Material and Method AnimalsFourty Wistar male rats weighing 200 to 250 gm at the beginning of the experiments were used. This experiment was reviewed by the Committee on Ethics in Animal Experiments of the Ankara University Faculty of Medicine. Before each operation, animals were fasted overnight with free access to water.Experimental Study The rats were divided into three groups:control group (sham laparatomy, n=10), 70% hepatectomy group (n=15), and 85% hepatectomy group (n=15). Anesthesia was induced by subcutaneous injection of a mixture of ketamine hydrochloride 100 mg/kg and xylazine 25 mg/kg. The abdomen was opened, the liver was mobilized and gently manipulated, and abdomen was closed in control group. Seventy percent hepatectomy included removal of left lateral and median lobes. Eighty-five percent hepatectomy included removal of left lateral,median,caudate anterior,and part of right superior lobes (according to Anderson and Higgins).All rats underwent relaparotomy 24h later. After fixation in formalin buffered solution, remnant liver tissues harvested for histopathologic and immunohistochemical examination. All the blood samples for biochemical analyses were drawn with cardiac puncture.All rats underwent relaparotomy 24h later. Remnant liver tissues were harvested for histopathologic analyse and TUNEL assay. HistopathologyAfter washing out the blood from the right lobe of the liver by infusion of normal saline via portal vein cannula, 0.2 mM trypan blue (Sigma Chemical Co., St. Louis, MO, USA) was infused for 10 minutes through the same cannula. Excess dye was removed by perfusion of normal saline for an additional 5 min. Then livers were perfused with 1% paraformaldehyde for 6 min., and fixed tissue was embedded in paraffin and processed fo