사염화탄소, Dimethylnitrosamine, Thioacetamide의 3가지 시약과 쥐에게 간섬유증을 유도하는데 이용되는 담관결찰로 인한 조직병리학적 변화의 비교
Comparison of Histopathological Changes on the Three Drugs of Carbon Tetrachloride, Dimethylnitrosamine, Thioacetamide, and Bile Duct Ligation used for Induction of Liver Fibrosis in Rat
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Abstract
This study was carried out to compare the histopathological differences of liver lesions in carbon tetrachloride (CCI4), dimethylnitrosamine (DMN), thioacetamide (TAA) and bile duct ligation (BDL)-induced rats. CCl4, DMN and TAA were administered intraperitoneally and conducted bile duct ligation for 4 weeks to induce hepatic fibrosis. Indices of liver cell injury (steatosis, hydropic degeneration, bile duct hyperplasia, hemorrhage & hemosiderin deposition), the extent of liver fibrosis (fibrotic area) and the rate of regeneration (number of PCNA-positive cells) were investigated in each group. Liver tissues were stained with hematoxylin-eosin (HE), sirius red, prussian blue and immunostained with α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), proliferative cell nuclear antigen (PCNA), and quantified using a computerized image analysis system. Liver cell steatosis was significantly increased in CCl4 and TAA groups, and hydropic degeneration and bile duct hyperplasia were significantly increased in TAA and BDL groups when compared with that in normal control, respectively. Fibrosis area was significantly increased in all four groups, especially in CCl4 group. Correlation between α-SMA and TGF-β1 expressions in four groups was good. Hemorrhage area in liver parenchyma was significantly increased in DMN group only when compared with that in normal control, while hemosiderin deposition area was significantly increased in TAA and BDL groups as well as DMN group. The Number of PCNA-positive cells was significantly increased in all four groups, especially in TAA group. These results indicate that the duration and methods of hepatotoxic drug treatment are very important factors to make plans for animal experimentation on the induction of hepatic fibrogenesis in rats.
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