| Hepatic injury and hepatic fibrosis is world disease, There are 100000 people who death from this kind of disease in the world. Many factors can cause hepatic injury, including truma hepatic injury and chemical hepatic injury and virus hepatic injury. Research has shown that mechanism of hepatic injury is related to virus and injury induced from mechanism of body immunity . Histology character of inflammation is soakage of inflammatory cell.Recombinant human elafin is an elastase inhibitor with the Mr of 6kDa, and its gene located on chromosome 20. Elafin is the specific inhibitor of neutrophil elastase (NE), pancreatic elastase and proteinase 3.Elafin inhibits the activity of serine proteases, and then plays its role in adjusting the release of inflammatory meditors, inhibiting the transendothelial migration of leukocytes and the activation of hemacytes, reducing the infiltration of inflammatory cells and the release of tissue toxic substances, etc. From this we can see that elafin display its multi-layered anti-inflammatory effect. Elafin has attracted clinic widespread attention by its protective effect through anti-inflammatory.This paper established the model of rat acute hepatic injury by injection of carbon tetrachloride and D-galactosamine, and then we observed the protective effects of elafin on rats acute hepatic injury by biochemical and pathological changes of rats after elafin treatment. In the last we will discuss the mechanism of hepatic injury.Experiment 1 Protective effect of recombinant human Elafin a on acute liver injury induced by carbon tetrachloride in rats.Sixty rats were randomly divided into six groups: the blank group (NS group), the model group (CCl4 group) and the high-dose elafin group, the medium-dose group, the low-dose group, the positive control group, with 10 rats in each group. In addition of CCl4 , the high,medium,low-dose elafin groups received intravenous infusion of (2μg/kg,4μg/kg,8μg/kg)elafin, while the control and model group received the same amount of saline, with the period of every day one infusion , continuously 7 times . 48 hours after the last injection, the blood samples from the abdominal aorta were obtained, then the serum ALT,AST,CAT,GSH,NO content were detected; After the liver tissue homogenate, the tissue protein, SOD, MDA content were detected; pathological changes of rats liver tissue were observed and its morphological structure were observed by electron microscope.1. Effects of Elafin on liver weight ratio in CCl4 liver injury Compared with the model control,the liver weight ratio decreased,but it has no statistical meaning in the groups of rats ated with Elafin.2. Effects of Elafin on ALT,AST of serum in CCl4 liver injuryThe activity of serum ALT,AST in model group were increased .The rats treated with Elafin with different dosage exhibited that the activity of ALT,AST in blood serum were decreased in different degree(P<0.01).3. Effects of Elafin on SOD,MDA of tissue in CCl4 liver injuryCompared with model group , the content of liver tissue SOD in elafin(low dose, medium dose, high dose) groups increased significantly(p<0.01). while the content of MDA decreased significantly(p<0.01). The effect of high dose group is almost equal to DGI group.4. Effects of Elafin on CAT,GSH of serum in CCl4 liver injuryCompared with model group , The activity of serum CAT,GSH in elafin(low dose, medium dose, high dose) groups decreased significantly(p<0.01). The effect of high dose group is almost equal to DGI group.5. Effects of Elafin on NO of serum in CCl4 liver injuryCompared with model group , The activity of serum CAT,GSH in elafin(low dose, medium dose, high dose) groups decreased significantly(p<0.05, p<0.01). The effect of high dose group is almost equal to DGI group.6. Effects of Elafin on expression of tissue TNF-αin CCl4 liver injuryThe expression of TNF-αprotein in tissue was determined by immunohistochemistry .The results showed that after treated with Elafin, expression of TNF-αand protein in tissue was significantly reduced compared with model group(P<0.01).The results have shown that Elafin has the protective effect through inhibiting the inflammatory process.7. Effects of Elafin on Pathology of tissue in CCl4 liver injuryUnder light microscopy,the extent of hepatic tissue damage caused by carbon tetrachloride, including necrosis and hydropic swelling of hepatocytes and inflammatory cell infiltration,were decreased in the groups treated with elafin with different dosage.Experiment 2 Protective effect of recombinant human Elafin a on acute liver injury induced by D-GalN in rats.Sixty rats were randomly divided into six groups: the blank group (NS group), the model group (D-GalN group) and the high-dose elafin group, the medium-dose group, the low-dose group, the positive control group, with 10 rats in each group. In addition of D-GalN, the high,medium,low-dose elafin groups received intravenous infusion of (2μg/kg,4μg/kg,8μg/kg)elafin, while the control and model group received the same amount of saline, with the period of every day one infusion , continuously 7 times . 48 hours after the last injection, the blood samples from the abdominal aorta were obtained, then the serum ALT,AST,ALP,GSH,NO,ALB,T-BIL were detected; After the liver tissue homogenate, the tissue protein,SOD,LPO content were detected; pathological changes of rats liver tissue were observed and its morphological structure were observed by electron microscope.1. Effects of Elafin on liver weight ratio in D-GalN liver injuryCompared with the model control,the liver weight ratio decreased,but it has no statistical meaning in the groups of rats ated with Elafin.2. Effects of Elafin on ALT,AST of serum in D-GalN liver injuryCompared with model group , The rats treated with Elafin with different dosage exhibited that the activity of ALT,AST in blood serum were decreased in different degree(P<0.01). The effect of high dose group is almost equal to DGI group.3. Effects of Elafin on SOD,MDA of tissue in D-GalN liver injuryCompared with model group , the content of liver tissue SOD in elafin(low dose, medium dose, high dose) groups increased significantly(p<0.01). while the content of MDA went down significantly(p<0.01). The effect of high dose group is almost equal to DGI group.4. Effects of Elafin on NO,GSH of serum in D-GalN liver injuryCompared with model group , The activity of serum NO,GSH in elafin(low dose, medium dose, high dose) groups significantly(p<0.01). The effect of high dose group is almost equal to DGI group.5. Effects of Elafin on ALB,A/G of serum in D-GalN liver injuryCompared with model group , The activity of serum ALB,A/G in elafin(low dose, medium dose, high dose) groups increased significantly(p<0.05, p<0.01). The effect of high dose group is almost equal to DGI group.6. Effects of Elafin on expression of tissue NF-κB p65 in D-GalN liver injuryThe expression of NF-κB p65 protein in tissue was determined by immunohistochemistry .The results showed that after treated with Elafin, expression of NF-κB p65 and protein in tissue was significantly reduced compared with model group(P<0.01).The results have shown that Elafin has the protective effect through inhibiting the inflammatory process.7. Effects of Elafin on Pathology of tissue in D-GalN liver injuryUnder light microscopy,the extent of hepatic tissue damage caused by carbon tetrachloride, including necrosis and hydropic swelling of hepatocytes and inflammatory cell infiltration,were decreased in the groups treated with elafin with different dosage.In conclusion, elafin can prevent and cure the acute liver injury induced by CCl4 and D-GalN.
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