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Gene-CYP11B2 expression in rat liver in hepatic fibrogenesis induced by CCl4
1PLA Institute for Digestive Diseases, Nanfang Hospital, First Medical University of PLA, Guangzhou 510515, China.
Objective:
To identify aldosterone synthase gene-CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antisterone.
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/100 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 times a week. Antisterone equivalent to 20 mg.kg-1.d-1 was given intragastrically (ig). In the malotilate group (n = 40), the rats were injected with 40% CCl4 (0.25 ml/100 g) subcutaneously three times a week. Malotilate 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 out. The area of collagen was examined with an Image Analyse System. Expression of the aldosterone synthase gene, CYP11B2 mRNA, in fibrotic and normal liver was detected by means of reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization.
Results:
In situ hybridization and RT-PCR showed that the expression of CYP11B2 mRNA, which localized in the endoplasm of hepatic stellate cells (HSCs), was up regulated when fibrogenesis occurred. Histological observation indicated that the grade of fibrosis and the area of collagen in the antisterone group were less than those in model group before 6 weeks (P < 0.05). There was no significant difference between the antisterone and malotilate groups (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 antisterone and model groups (P > 0.05).
Conclusions:
The expression of CYP11B2 mRNA is up regulated in fibrotic liver. Antisterone can have a partial fibrogenesis-inhibiting effect in the early stages.