Sequential study of liver collagen fibers in diethylnitrosamine-induced hepatocarcinogenesis in rats

Abstract

Objective To observe the sequential changes of collagen fibers in rats with diethylnitrosamine(DEN)-induced hepatocellular carcinoma(HCC),so as to provide a reference for pathogenesis research of HCC.Methods Fifty male Wistar rats,weighing 100-120g,were randomly divided into normal group and HCC model group.The model group was intraperitoneally administered with 50mg/kg DEN(0.1mL),twice a week for 4weeks,then once a week for another 10weeks.The control group was given normal saline(0.1mL)in the same manner.Finally the rats were sacrificed;the normal and diseased liver tissues were observed by H-E,Masson and argyrophilic fiber staining.The expression of collagen typeⅠand typeⅢ mRNA was detected by fluorogenic quantitative PCR;the expression of matrix metalloproteinase(MMP)was examined by gelatinases spectrometry.Results Cirrhosis was found in rats 5weeks after treatment with DEN and HCC was induced 14weeks after DEN treatment;collagen deposition in liver tissues increased in a progressive manner,and the collagen contents in the HCC tissues was greatly less than that in the adjacent tissues,showing a decreasing trend.The contents of MMP-2and MMP-9in the HCC and adjacent tissues had opposite changes compared with collagen.Conclusion Collagen deposition in cirrhosis liver tissue is increased during the process of DEN-induced HCC,but it is decreased in HCC tissues in aprogressive manner,which indicates that collagen might be degraded during the progression from cirrhosis to HCC.