Gene-CYP11B2 expression in rat liver in hepatic fibrogenesis induced by CCl4

Objective To identify aldosterone synthase gene-CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antis terone. Methods 160 Wistar rats weighing about 250 g were divided into 4 groups. In the model group (n = 40), the rats were injected with 40% CCl4 (0.25 ml/10 0 g) subcutaneously three times a week. In the antisterone group (n = 40), the rats were injected with 40% CCl4 (0.25 ml/100 g) subcutaneously three t imes a week. Antisterone equivalent to 20 mg . kg(-1) . d(-1) was given int ragastrically (ig). In the malotilate group (n = 40), the rats were injecte d with 40% CCl4 (0.25 ml/100 g) subcutaneously three times a week. Malotila te equivalent to 50 mg . kg(-1) . d(-1) was given ig. In the control group (n = 40), the rats were injected with olive oil only. After 2,4,6,8 and 10 weeks, animals were sacrificed, and morphological examination was carried o ut. The area of collagen was examined with an Image Analyse System. Express ion of the aldosterone synthase gene, CYP11B2 mRNA, in fibrotic and normal liver was detected by means of reverse transcriptase polymerase chain react ion (RT-PCR) and in situ hybridization. Results In situ hybridization and RT-PCR showed that the expression of CYP1 1B2 mRNA, which localized in the endoplasm of hepatic stellate cells (HSCs) , was up regulated when fibrogenesis occurred. Histological observation ind icated that the grade of fibrosis and the area of collagen in the antistero ne group were less than those in model group before 6 weeks (P < 0.05). The re was no significant difference between the antisterone and malotilate gro ups (P > 0.05). After that, however, the grade of fibrosis and the area of collagen in the antisterone group were higher than those in the malotilate group ( P < 0.05). There was no significant difference between the antister one and model groups (P > 0.05). Conclusions The expression of CYP11B2 mRNA is up regulated in fibrotic live r. Antisterone can have a partial fibrogenesis-inhibiting effect in the ear ly stages.