Cyclooxygenase- 2 과발현은 CCl-induced 간섬유증의 증가된 mast cells와 관련이 있다.
Cyclooxygenase-2 over-expression is associated with increased mast cells in CCl4-induced hepatic fibrosis
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Abstract
Cyclooxygenase(COX-2) is an inducible enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Over-expression of COX-2 has been reported to be associated with progressive hepatic fibrosis in chronic hepatic C infection and rat liver fibrosis induced by carbon tetrachloride(CCl4). Recently, it is well known that mast cell products can stimulate the proliferation of hepatic stellate cells and key players in liver fibrosis. But little is known regarding their role in CCl4-induced liver fibrosis in rat. Our aim was to investigate the relation between COX-2 expression and mast cells during liver fibrosis after CCl4 treatment. Thirty Wistar rats were divided into five groups (non-treated 0, 2, 4, 6 and 8-week after CCl4-treatment). Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to assess the expression of α-smooth muscle actin (α-SMA), collagen-1 and COX-2 in liver tissue from CCl4-treated rats. The density of collagen and mast cells were determined using a computerized image analysis system in liver sections stained with picrosirius red and toluidine blue, respectively. The expression levels of α-SMA, collagen-1 and COX-2 mRNA were significantly higher at 2 wk in CCl4-treated groups than non-treated group. The number of mast cells in liver tissues increased gradually from 2 wk to 6 wk depending on the fibrosis severity but decreased abruptly at 8 wk. The significant increase of collagen-1 and α-SMA mRNA expression in CCl4-treated rats was continued until 6 wk while the COX-2 mRNA was significantly decreased at 8 wk. These results suggest that increased mast cells are closely associated with COX-2 over-expression during hepatic fibrogenesis of CCl4-treated rats.
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