Effects Of Danshensu On RhoA/Rockâ…  Signaling Parthway In HSC

Objective: To investigate the role of Danshensu on the RhoA/RockⅠsignaling parthway in HSCs which were stimulated by FN, and to elucidate the anti-fibrotic molecular mechanism of Danshensu.Methods: The mice HSCs were isolated with collagenase in situ-liver recirculation perfusion and cultured in vitro.After stimulation of FN,HCSs were cultured in vitro with Danshensu(0.062 5～0.25 mmol/L)or Y-27632(30μmol/l) ,which is a specific RockⅠinibitor. The cell proliferation was assessed by MTT assay; the synthesis and secretion of collagenⅠwere examined by methods of immunohistochemistry and Enzyme Linked Immunosorbent Assay accordingly; the protein levels of RhoA,p-Mlc(Thr18/Ser19),and p-FAK(Tyr397) were analyzed by Western Blot.Results: FN promoted the proliferation of HSC significantly and provoked the synthesis and secretion of collagenⅠmarkedly, meanwhile the protein levels of RhoA,p-Mlc(Thr18/Ser19),and p-FAK(Tyr397) also increased. The interventions of Y-27632 and Danshensu could inhibite the above effects in HSC distinctly(p<0.05).Conclusion: The FN activates the RhoA/RockⅠsignal parthway and the intergin signal parthway in HSC; Interventing the RhoA/RockⅠsignal parthway might be involved with the effect of Danshensu that inhibits the HSC proliferation and decreases the synthesis and secretion of collagenⅠ;The down regulation of FAK by RockⅠis one of the anti-fibrosis mechanisms of Danshensu.