| Objectives: To investigate the effects of Danshensu on proliferation and activation of HSC-T6 cells,expression of Smad3 and Smad7 mRNA in HSC-T6 cells,and to elucidate the molecular mechanisms of Danshensu against hepatic fibrosis.Method: HSC-T6 stellate cell line was employed as the cell model for the following study. MTT colorimetric assay was used to detect proliferation of HSC-T6 cells treated with different concentration Danshensu for different time. Danshensu was tried to incubate HSC-T6 cells stimulated with TGF-β1,α-SMA protein expression of HSC-T6 cells was observed by Immunocytochemical staining method. HSC-T6 cells were treated with different concentration Danshensu for different time, the chang of Smad3 and Smad7 mRNA was observed by RT-PCR.Resultes:⑴Danshensu had an inhibition effect on the proliferation of HSC-T6 cells depended on the dose at the concentration of 0.25 mg/l～16 mg/l for 12 h,24 h or 48 h(P<0.05). The proliferation of HSC-T6 cells was almost completely inhibited at the concentration of 16 mg/l for 48 h(P<0.05).⑵Danshensu at the concentration of 0.5mg/l could downregulateα-SMA protein expression at 48th hour in HSC-T6 cells,with or without stimulation of TGF-β1(P<0.05),and the activation of HSC-T6 cells was then inhibited.⑶Danshensu could downregulate Smad3 mRNA expression in HSC-T6 cells induced by TGF-β1,those effects correlated with concentration of Danshensu ( P <0.05 ) . Danshensu also could upregulate Smad7 mRNA expression in HSC-T6 cells at earlier period(P<0.05).Conclusion: Danshensu could directly or indirectly modulate the mRNA expression of Smad3 and Smad7 in HSC. Danshensu could inhibit TGF-β1/TβR/Smads signaling pathway in HSC,and inhibit proliferation and activation of HSC. Those effects might be involved in the important mechanism of Danshensu against hepatic fibrosis.
|
PDF Full Text Request