The experimental study on mouse pristine hepatic fibrosis induced by different doses of alcohol

AIM: To explore the difference on formation mechanism and the pathology in the process of early liver fibration induced by two dose of ethanol. METHODS: 24 male KM mice were randomly divided into 3 groups which are control group, low dose of alcohol group and high dose of alcohol group, respectively. The mice treated with 8 g·kg^-1·d^-1 ethanol, 3 g·kg^-1·d^-1 ethanol by oral were killed 30 days later. The liver histomorphology,inflammation grade and fibration staging were observed and the areas of collagen per high power field were calculated by hematoxylin-feosin (HE) and Masson staining; the expression of Toll like receptor-4(TLR-4), α-smooth muscle actin (α-SMA) and content of transforming growth factor-β (TGF-β), nuclear factor-kappa B (NF-кB) protein, BMP and activin membrane-bound inhibitor (Bambi) mRNA were measured using immunohistochemistry, Western blotting, real-time quantitative polymerase chain reaction, respectively; apoptosis cell number was calculated by In Situ Nick-End Labeling (TUNEL). RESULTS: Different degree of fibration mice induced by ethanol appeared (P<0.01) and hepatic stellate cells (HSCs) in these mice liver were activated, meanwhile the apoptosis cell number increased too (P<0.01). The liver fibration at high dose group was more serious than that at low dose group mice, and the number of apoptosis cells showed the same trend as fibration, but the content of Bambi mRNA in high dose group down regulated compared to that in low dose group (P<0.05). On the other hand, the expression of TLR-4 enhanced in low dose group while decreased in high dose group compared to control group (P<0.01). CONCLUSION: The mechanism of early mouse liver fibration induced by two dose of alcohol is different. Apoptosis may be more responsible for the liver fibration induced by high dose alcohol than TLR-4 pass way, and there is a TLR-4 independent pathway to down-regulate the Bambi that probably is one of the reasons that the fibrosis is more serious in the high dose group.