The Effect Of Tetramethylpyrazine On TGF-β₁ -induced CTGF Expression Via P38MAPK Pathways In Hepatic Stellate Cells

OBJECITVE: 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).TMETHODS: HSCs were cultured in vitro, stimulated by transforming growth factorβ1 (TGF-β1, 5μg/L), and then, intervened by Tetramethylpyrazine and p38MAPK specific blocker SB203580. The expressions of CTGF and typeⅠcollagen mRNA were measured by reverse transcription polymerase chain reaction. The phosphorylation of p38mapk was assessed by Western blotting.RESULTS: Compared with the control group, TGF-β1-induced CTGF and typeⅠcollagen gene expression were obviously increased (P < 0.01). CTGF and typeⅠcollagen expressions appeared decreased in varying degrees after the intervened by Tetramethylpyrazine and SB203580. But the Tetramethylpyrazine group and Tetramethylpyrazine + SB203580 inhibited the expression of typeⅠcollagen and CTGFmRNA 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.Howeve, the differences between the SB203580 group and Tetramethylpyrazine + SB203580 had no significance(P>0.05).CONCLUSION:Accordingly,it is supposed that Tetramethylpyrazine inhibits TGF-β1-induced CTGF gene expression, blocks typeⅠcollagen mRNA synthesis,and its mechanism may be related to inhibition p38MAPK signaling pathways.The role of anti-fibrosis may be multi-target.