Effects Of Pretreatment With Glutathione On The Glucose Metabolism During The Hepatic Ischemia/Reperfusion Injury In Rats

Objective1. To observe the effects of pretreatment with glutathione on the disturbance of glucose metabolism during the hepatic ischemia/reperfusion injury (HIRI) in rats.2. To investigate the possible mechanism of the disturbance of glucose metabolism during the hepatic ischemia/reperfusion injury (HIRI) in rats.Methods1. Experimental design: Seventy-eight healthy SD rats weighing 260~340 g were kept under constant environment conditions with a 12 h light-dark cycle, and freely accessed to food and water. The rats were randomly divided into ischemia/reperfusion group (group IR), glutathione group (group GSH) and control group (group C) with 26 rats each.2. Animal model: The rats were fasted 12 h but freely got water prior to operation, and were anesthesiaed by 1% sodium pentobarbital (40 mg/kg) in the intraperitoneal injection. A midline incision was made to expose the liver. Portal vein and liver artery that drain blood to middle and left lobes of the liver were dissected. The 70% HIRI model was established via blocking the blood flow of the middle and left lobes 40 min with a non-invasive vessel clamps in group IR and group GSH. In the group GSH, glutathione was administered via vena jugulars 10 min before ischemia. In the group IR, normal saline was administered via vena jugulars 10 min before ischemia. In the group C,normal saline was administered via vena jugulars 10 min before the abdomen closed.3. Test items: The concentrations of blood glucose (BG) and plasma insulin, the activity of superoxide dismutase(SOD), the levels of malondialdehyde(MDA) were determined at 2 h or 6 h after reperfusion in 16 rats of each group. Hyperglycemic clamp test was performed at 2 h or 6 h after reperfusion in another 10 rats of each group. After hyperglycemic clamp test, the insulin secretion level, the glucose metabolism rate and the insulin sensitivity index were determined or calculated.Results1. Ischemia for 40 min and reperfusion for 2 h or 6 h ,compared with those in group C, the concentrations of BG and the levels of MDA were significantly higher in group IR, but the activity of SOD and the concentrations of plasma insulin were remarkably lower. After pretreatment with glutathione, the concentrations of BG and the levels of MDA were significantly lower, the activity of SOD and the concentrations of plasma insulin were remarkably higher in group GSH. than those in group IR.2. The hyperglycemic clamp test showed that the insulin secretion level, the glucose metabolism rate and the insulin sensitivity index in group IR were obviously lower than those in group C.Compared with those in group IR, the levels of insulin secretion, the glucose metabolism rate and the insulin sensitivity index were higher in group GSH. Conclusion1. Glutathione pretreatment has a protection against the disturbance of glucose metabolism during the hepatic ischemia/reperfusion injury (HIRI) in rats.2. The mechanism of protection of glutathione during the hepatic ischemia/reperfusion injury (HIRI) in rats may be associated with its scavenging of oxygen free radical and inhibition of lipid peroxidation.