| Objective:In the hope of providing new treatment clues,We established mouse model of acute liver failure and rat model of liver fibrosis and abserved the effect of protection and therapy through granulocyte colony-stimulating factor(G-CSF), hepatocyte growth-promoting factors(pHGF) and their combination on these two models.Methods:(1)A mouse model of acute liver failure was induced by an intraperitoneal single dose of CC14(5mL/kg)30%vol/vol in mineral oil. Totally65experimental mices were randomly divided into five groups. At24h,2h and Oh before CC14induction,group-A (n=15) were treated with rhG-CSF(300μg/kg) by intraperitioneal injection; group-B (n=15) were treated with pHGF(15mg/kg) by intraperitioneal injection; group-C (n=15) were treated with rhG-CSF (300μg/kg)and pHGF(15mg/kg) by intraperitioneal injection; group-D (n=15) were treated with saline by intraperitioneal injection;group-E(n=5) were treated with saline by intraperitioneal injection but weren’t treated with CC14induction. At24h after CC14induction,all5mices of each group were randomly choosed and sacrificed to assess liver function and hepatic pathological changes,others were observed for survival rate.The general condition, survival rate, recovery of liver function and hepatic pathological changes were compared among each groups.(2) A rat model of liver fibrosis was induced by intraperitoneal administration of thioacetamide (250mg/kg,twice per week for6weeks). All the30Sprague Dawley rats (SD rats) were divided into experiment model group (n=26) and control group(n=4).After six weeks,four rats (model group)were randomly selected from26experimental model rats and sacrificed to assess the degree of liver fibrosis.If the model of liver fibrosis was confirm to be successful, the other experimental model rats would be divided into four groups:group-A(n=6) were treated with rhG-CSF(10μg/kg) by intraperitioneal injection; group-B (n=6)were treated with pHGF(8.4mg/kg) by intraperitioneal injection;group-C(n=6) were treated with rhG-CSF(10μg/kg) and pHGF(8.4mg/kg) by intraperitioneal injection; group-E(n=4) were treated with saline by intraperitioneal injection. The general condition,recovery of liver function and hepatic pathological changes were compared among each groups.Results:(1) The CC14-induced model of acute liver failure:all mices of the model group(group-D)were died within120hours after CC14induction,massive necrosis of hepatocellular parenchyma were observed histologically and liver cell regeneration were not obvious. Compared with nomal group, at24hours after CC14induction serum levels of ALI、AST were increased remarkably (2294.8±403.6) u/1vs58.1±26.4) u/l、(5045.6±1690.9)u/l vs (220.6±50.3)u/l(p<0.05). Compared with the model control group, the general condition of every pretreatment group were markedly improved, the survival rate of G-CSF、pHGF、G-CSF+pHGF group were50%(5/10).50%(5/10)、60%(6/10),respectively and markedly improved(p<0.05), markedly lessened the histological damage,significantly lowered the serum levels of AL、AST at24hours after CC14induction:(1105.4±81.1) u/l、(894.3±40.5) u/l;(1559.1±197.2) u/l、(1250.4±254.6) u/1;(1152.4±110.4) u/l、(863.5±42.9) u/1respectively (p<0.05).But at120h after CC14induction, survival rate, the histological improvement and serum transaminase level between the pretreatment groups was found to be of no significant difference(p>0.05).(2) Compared with control group, the general state of health of the mouse of thioacetamide induction for6weeks was much worse and the serum level of ALT increased significantly (746.5±344.0) u/1vs (48.2±7.5) u/l (p<0.05),the hepatic inflammation activity scores and the hepatic fibrosis degree scores was significantly increased (12.15±2.55vs0.20±0.08,7.65±2.01vs0.00±0.00)(p<0.01), the stagings of liver fibrosis in histology were from S2to S3. Compared with control group, the serum level of ALT、the hepatic inflammation activity scores and the hepatic fibrosis degree scores of every treatment group was found to be of no significant difference(p>0.05), the stagings of liver fibrosis were up to S1. There was also no significant difference between treatment groups (p>0.05).Conclusions:(1) A mouse model of acute liver failure can be successfully induced by an intraperitoneal single dose of CC14(5mL/kg)30%vol/vol in mineral oil.(2) G-CSF, pHGF and the their combination therapy exerts a protective effect against carbon tetrachloride (CC14) induced acute liver failure respectively, but the protective effect is not significantly different between three pretreatment groups.(3) None of G-CSF, pHGF or the combination therapy exerts a obvious curative effect against the thioacetamide-induced rat model of liver fibrosis. |
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