Effect of oxymatrine on hepatic gene expression profile in experimental liver fibrosis of rats.

OBJECTIVE

To investigate the effects of oxymatrine on hepatic gene expression profile in a rat model of liver fibrosis.

METHODS

Forty healthy male SD rats were randomly divided into three groups, a normal group (n=8), a model group (n=16), and an oxymatrine treatment group (n=16). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl(4)). The rats in the treatment group received oxymatrine via celiac injection at a dosage of 40 mg/kg once a day at the same time. The rats in the model and normal groups received saline at the same dosage via celiac injection. Serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AKP), hyaluronic acid (HA), and laminin (LN) were assayed. The deposition of collagen was observed with HE and Masson staining. Effect of oxymatrine on hepatic gene expression profile was detected by oligonucleotide microarray analysis with Affymetrix gene chip rat U230A. Quantitative real-time polymerase chain reaction (QRT-PCR) was carried out to confirm the expression changes of six genes.

RESULTS

Oxymatrine significantly improved liver function, lowered serum levels of HA and LN, and decreased the degree of liver fibrosis, compared with the model group (P<0.05). A total of 754 differentially expressed genes were identified by gene chip between the model group and the normal group, among which 438 genes increased and 316 genes decreased over two folds. Compared with the model group, 86 genes were downregulated markedly in the oxymatrine group (P<0.05), including collagen I and other genes related to extracellular material (ECM), integrin signal transduction genes, early growth response factor genes, and proinflammatory genes; 28 genes were upregulated significantly (P<0.05), including cytochrome P450 (CYP450) superfamily genes, glycolipids metabolism and biological transformation related genes. Six genes were confirmed with QRT-PCR, consistent with the result from microarray.

CONCLUSION

Oxymatrine could affect the expression of many functional genes and may be useful in the prevention and treatment of liver fibrosis.