Abstract:

BACKGROUND: Previous studies demonstrated that Tetramethylpyrazine can anti-hepatic fibrosis via inhibiting hepatic stellate cells proliferation, blocking the synthesis of type Ⅰ, Ⅲ collagen, as well as down-regulating the expression of connective tissue growth factor (CTGF), however, the detail mechanisms remains unclear.
OBJECTIVE: To investigate the effects of Tetramethylpyrazine on expression of CTGF and the role of p38 mitogen-activated protein kinase (p38MAPK) signal pathway in hepatic stellate cells (HSCs).
METHODS: HSCs were cultured in vitro, stimulated by transforming growth factor β1 (TGF-β1, 5 μg/L), and then, intervened by Tetramethylpyrazine and P38MAPK specific blocker SB203580. The expressions of CTGF and type Ⅰ collagen mRNA were measured by reverse transcription polymerase chain reaction. The phosphorylation of p38 MAPK was assessed by Western blotting.
RESULTS AND CONCLUSION: Compared with the control group, TGF-β1-induced CTGF and type Ⅰ collagen gene expressions were obviously increased (P < 0.01). CTGF and type Ⅰ collagen expressions appeared decreased in varying degrees after the intervened by Tetramethylpyrazine and SB203580. But the Tetramethylpyrazine and Tetramethylpyrazine + SB203580 inhibited the expression of type Ⅰ collagen and CTGF mRNA higher than that of SB203580. Tetramethylpyrazine and SB203580 also significantly inhibited the phosphorylation p38MAPK protein expression (P < 0.01). The inhibitory effects were more obviously in the SB203580 and Tetramethylpyrazine + SB203580 groups. However, the differences between the SB203580 group and Tetramethylpyrazine + SB203580 had no significance (P > 0.05). Accordingly, it is supposed that Tetramethylpyrazine inhibits TGF-β1-induced CTGF gene expression, blocks type Ⅰ collagen mRNA synthesis, and its mechanism may be related to inhibition p38 MAPK signaling pathways. The role of anti-fibrosis may be multi-target.