Abstract: Objective:To investigate the inhibitory effect of dehydroandrographolide (DA) on the hepatocyte apoptosis induced by carbon tetrachloride (CCl₄) in the hepatic fibrosis model mice, and to elucidate its possible mechanism. Methods:A total of 30 male C57BL/6J mice aged 6-8 weeks were randomly divided into control group, model group and treatment group;there were 10 mice in each group. Except the normal control group, the mice in other two groups were intraperitoneally injected with 20% CCl₄ 2.0 mL·kg^-1, three times a week;the hepatic fibrosis models were establised. The mice in control group were given the same volume of olive oil. The mice in treatment group were intragastrically given 100 mg·kg^-1 DA,three times a week; while the mice in control group and model group were given the equal volume of normal saline. Four weeks later, 24 h after the last administration, the eyeball blood was taken, the marrow was broken, and the liver was taken. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the mice in various groups were detected; the activities of superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) in liver tissue of the mice in various groups were detected. The pathological performance of liver tissue of the mice in various groups were observed by HE staining and Sirius red staining. Western blotting method was used to detect the levels of 8-oxoguanine DNA glycosylase 1 (Ogg1), Caspase-3, Bcl-2-associated X protein(Bax), and B-cell lymphoma-2 (Bcl-2) proteins in liver tissue of the mice in various groups. The expression levels of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) proteins in liver tissue of the mice in various groups were observed by immunohistochemistry. Results:Compared with control group, the activities of serum ALT and AST and the level of MDA in liver tissue of the mice in model group were significantly increased (P<0.05), and the activity of SOD in liver tissue was significantly decreased (P<0.05). Compared with model group, the activities of ALT and AST in serum and the level of MDA in liver tissue of the mice in treatment group were significantly decreased (P<0.05), and the activity of SOD in liver tissue was significantly increased (P<0.05). The HE staining and Sirius red staining results showed that compared with model group, the inflammatory cell infiltration and collagen deposition in liver tissue of the mice in treatment group were significantly improved. Compared with control group, the expression levels of Ogg1, Caspase-3, Bax, TGF-β1,α-SMA and Bcl-2 proteins in liver tissue of the mice in treatment group were significantly increased (P<0.05); compared with model group, the expression levels of Ogg1, Caspase-3, Bax, TGF-β1 and α-SMA proteins in liver tissue of the mice in treatment group were significantly decreased (P<0.05), and the expression level of Bcl-2 protein was significantly increased (P<0.05). Conclusion:DA has a protective effect in the mice with hepatic fibrosis induced by CCl₄, which might be related to reducing oxidative stress injury, inhibiting hepatocyte apoptosis and reducing hepatic stellate cell activation.

Key words: dehydroandrographolide, hepatic fibrosis, apoptosis, hepatic stellate cells