Establishment and dynamic observation of rat model of liver fibrosis induced by complex factors

Objective:To establish the model of liver fibrosis(ALF) in rats induced by complex factors,and observe dynamicly its hepatic fibrosis lesions.Methods:54 healthy male rats were divided randomly into two groups:control group(n=9) and liver fibrosis group(n=45).The rats in the liver fibrosis group were given intraperitoneal injection of swine serum,subcutaneous injection of CC14 and gastric perfusion alcoho twice a week,and were fed with high fat food daily to induce ALF.During induction process,the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total protein(TP),albumin(Alb),Hyaluronic acid(HA),laminin(LN),transforming growth factor beta1(TGF-β1),matrix metalloproteinases(MMP-2,MMP-9,MMP-13),matrix metalloproteinases inhibitory factors(TIMP-1,TIMP-2) and histopathological changes of liver tissue were observed at the 2th,4th,6~10th week repectively.Results:From the beginning of the 2nd week,the ALT and AST level in serum of the model group went up,and ALT,AST level had significant differences compared with those in control group respectively at each time point;the serum levels of HA and LN group went up gradually,At the 7~10th week,compare with control group,there had significant differences;the serum levels of MMP-2 went up gradually,At the 4 th week and 6~10th week,compare with control group,there had significant difference;the serum levels of MMP-13 went down gradually from the 6th week,and was lower than that of control group at the 9th and 10th week;the serum levels of TIMP-1,TIMP-2 went up gradually from the 2th week,and At the 4th week and 6~10th week,compare with control group,there had significant difference for TIMP-1,TIMP-2 was higher than that of control group at the 7~10th week;the serum levels of TGF-β1 of model group was higher than that of control group at each time point.The histopathological changes of liver tissue shows:the hepatocyte of the rats in the liver fibrosis group were vacuolar degeneration widely,Fibroblast hyperplasia were founded between portaltracts.Collagen fibers were founded between hepatic lobules.That is typical change of ALF.At the 8th week,pseudolobuli were founded,cirrhosis was formed.Conclusion:It is a successful way to induce ALF in rats by complex factors including alcohol,swine serum,high fat diet and CC14 for 6 weeks.Moreover,HA,LN,TGF-β1,MMP-2,TIMP-1 and TIMP-2 in serum can reflect preferablely hepatic fibrosis lesions of rat as good targets.