TITLE Comparison Of The Effects Of The Pretreatment And Treatment With RhIL-11on Acute Liver Failure Induced By D-galactosamine

ObjectiveTo compare the effects of the pretreatment and treatment with recombinant human interleukin-11(rhIL-11) on acute liver failure induced by D-galactosamine (D-GalN).MethodsThe SD male rats were randomly divided into five groups:control, model, pretreatment, treatment and repeated treatment groups. The acute liver failure model was established by intraperitoneal injections with D-GalN (1400mg/kg). The pretreatment group was injected subcutaneously with rhIL-11(500μg/kg)2h before the D-GalN injection; The treatment group was injected subcutaneously with rhIL-11(500μg/kg)2h after D-GalN injection; The repeated treatment group was injected subcutaneously with rhIL-11(500μg/kg)2and24h after the D-GalN injection. At48and72h after the D-GalN injection,5rats from the repeated treatment group were sacrificed; At24h,5rats from the control group were sacrificed; At24,48and72h after the D-GalN injection,5rats from model, pretreatment and treatment groups were sacrificed. The symptoms of the rats were observed. Liver injury was assessed by serum ALT and AST levels and by histological analysis. The percentage of PCNA+cells in the liver tissue was evaluated by immunohistochemistry. Heme oxygenase-1(HO-1) activity was evaluated by western blot. In each group except the control group,10rats were used to observe the survival rate72h after the D-GalN injection.Results1. After intraperitoneal injection of D-GalN, the rats were induced obviously acute liver failure, as demonstrated by the mental malaise, anorexia, deep yellow urine and haematemesis, the increases in serum ALT and AST levels, the induction of large areas of necrosis, and the decreased survival rate.2. The symptoms of the rats:the rats were induced obviously acute liver failure in the model, treatment and repeated treatment groups, such as mental malaise, anorexia, deep yellow urine and haematemesis. Some rats in the pretreatment group had mental malaise and poor activity levels, but most rats in the pretreatment group were similar to the control group.3. The survival rate:The survival rates in the model, treatment and repeated treatment groups were50%,50%and30%, respectively,72h after the D-GalN injection. There was no significant difference among these three groups. The survival rate in the pretreatment group was90%, which was significantly higher than those in the model, treatment and repeated treatment groups.4. The serum levels of ALT and AST:The serum ALT and AST levels in each group (except the control group) increased at24h after the D-GalN injection and reached a peak at48h. The serum ALT and AST levels in the model, treatment and repeated treatment groups were significantly higher, and had no significant difference among them. The serum ALT and AST levels in the pretreatment group were significantly lower than those in the model group, treatment and repeated treatment groups at each time point, but were not significantly different compared with the treatment group at24h.5. The liver histopathology:The liver tissue changed obviously in the model, treatment and repeated treatment groups, and their pathology showed a disordered arrangement of the hepatic lobule structure, inflammatory cell infiltration and large necrosis. Most liver tissue had no change in the pretreatment group, and their pathological injuries were less severe than the model, treatment and repeated treatment groups.6. The percentage of PCNA+cells in the liver tissue:The percentage of PCNA+cells in the model group began to increase24h after the D-GalN injection, reached a peak at48h, and returned to the normal level at72h. The percentage of PCNA+cells in the pretreatment, treatment and repeated treatment groups increased gradually from24to72h, and were significantly higher than model group at72h. There was no significant difference among the three groups.7. The expression of HO-1in the liver tissue:The expression of HO-1in the control group was not detected. The expression of HO-1in the model group increased gradually from24to72h after the D-GalN injection. At48h, the expression of HO-1in the treatment and repeated treatment groups had no significantly different compared with the model group. But the expression of HO-1in the pretreatment was significantly lower than the model, treatment and repeated treatment groups.ConclusionsThe pretreatment with rhIL-11can obviously reduce acute liver failure and protect the liver. In contrast, the treatment with rhIL-11cannot reduce acute liver failure or protect the liver. The mechanism responsible for this difference needs further experimental confirmation.