| Backgrounds and PurposesThe ischemia-reperfusion(I/R) injury is an important cause of liver damage during surgical procedures including hepatic resections and liver transplantation. Liver steatosis is popular among people, affecting about 25% of donors for liver transplantation and 20% of patients undergoing liver resection. It can be caused by obesity, ethanol toxicity, or variety of metabolic disorders(such as diabetes mellitus, hyperlipemia). Hepatic steatosis is a major risk factor after liver surgery because steatotic livers tolerate poorly to I/R injury. Fatty livers are extremely sensitive to the deleterious effects of ischemia-reperfusion injury. The occurrence of postoperative liver failure after hepatic resection in a steatotic liver exposed to 60 min of vascular clamping has been reported. Moreover, fatty infiltration of a donor liver is a well-known risk factor for the development of graft dysfunction and in some cases graft failure after transplantation. However, the precise mechanism underlying increased vulnerability of fatty livers to I/Rinjury is still not fully understood. Current opinions suggest that the enhanced I/Rinjury IN fatty livers may be attributed to 1) fat solidification during organ preservation and hepatocyte disruption during reperfusion;2) enhanced lipid peroxidation; 3) increased damage to the sinusoidal microcirculation and increased leukocyte adhesion to the sinusoidal endothelial cells; 4) increased Kupffer cell activation; 5) deterioration of mitochondria ATP synthesis; and 6) decreased antioxidant defenses of the fat-laden hepatocytes. In 1986, Murry et al. discovered that a short period of ischemia and reperfusion led to an unexpected resistance of myocardium to a subsequent prolonged ischemia. The phenomenon, called ischemia preconditioning (IPC), has been subsequently documented in several organs, including cerebrum, spinal cord, optomein , Skeletal muscles , liver and lung.IPC is a potential therapeutic strategy, which may increase the tolerance of normal liver to ischemia-reperfusion injury demonstrated in animals as well as humans. But the mechanism of the preconditioning effect in the liver remains uncertain. Current thinking suggests that the protective effect may be attributed to 1) depresses Cellular necrosis and apoptosis; 2) protects the sinusoidal endothelial cells, improves liver microcirculation and decreases leucocytes adhere to platelet and endothelial cell; 3) decreases Kupffer cell activation and TNF, IL-1 release; 4) reduces acidosis and Na+ overload.Is ischemia preconditioning can increase the tolerance of fatty liver to hepatic ischemia-reperfusion injury or not? There is little investigation done at present in home and abroad. The present study were designed to make the fatty liver model by feeding a high-fat diet and aimed to evaluate whether ischemia preconditioning could be an effective strategy to reduce hepatic I/R injury in the presence of steatosis and to elucidate the underlying mechanisms of preconditioning on hepatic I/R injury in normal and steatotic liver.Materials and methodsExperimental animal and design: Seventy-two healthy Sprague-Dawley rats, weighing between 140 and 160 grams, were divided randomizedly into 8 groups. Rats in group 1-4 were fed a high-fat diet containing 10% lard, 2% Cholesterol, and 88%ordinary diet while rats in group 5-8 were fed ordinary diet.Water and food ad libitum until use and kept under constant environmental conditions with a 12-hour light-dark cycle. Group 1 and 5:control(NG1=9;NG5=10) rats were subjected to anesthesia and laparotomy. Group2 and 6: 1/11(NG2=9;NG6=10), rats were subjected to 40 minutes of partial ischemia followed by 90 minutes reperfusion. Group3 and 7: (NG3=8;NG7=8)ischemia preconditioning plus I/R (IPC-5+I/R), rats subjected to I/R were subjected to precious preconditioning induced by 5 minutes of ischemia and reperfusion. Group4 and 8: (NG4=8;NG8=10)( IPC-10+I/R), rats subjected to I/R were subjected to precious preconditioning induced by 5minutes of ischemia...
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