Inhibitory Effect Of Danshensu On Hepatic Stellate Cells Stimulated By Pdgf-Bb
Keywords
Danshenin, Hepatic Stellate Cells, Platelet-Derived Growth Factor-Bb, Collagen
Abstract
Objective To observe the effects of Danshensu on the activation and proliferation of rat hepatic stellate cells, the synthesis and secretion of type I and III collagen, and the expression of ERK1/2 and PI3K channel proteins stimulated by PDGF-BB, and to explore the molecular mechanism of Danshensu inhibiting liver fibrosis. Methods Different concentrations of Danshensu (0.250, 0.125, 0.062mmol/L), ERK channel specific inhibitor UO126 (20nmol/L) and PI3K channel specific inhibitor LY294002 (20nmol/L) were used to act on platelet-derived growth factors respectively. Rat hepatic stellate cells (HSC) were treated with PDGF-BB (10ng/ml) for 48 hours. HSC proliferation activity was detected by CCK8 method. Type I and III collagen synthesis was determined by immunochemical staining. Type I and III collagen were observed by enzyme-linked immunosorbent assay. Collagen secretion, Westernblot determination of ERK1/2, p-ERK1/2, AKT and p-AKT protein expression. Results After treatment with PDGF-BB10ng/ml, HSC proliferation increased significantly (0.139¡À0.009). Danshensu could inhibit the effect of PDGF-BB on stimulating HSC proliferation in rats, and the concentration of Danshensu increased with the increase of Danshensu concentration (0.062, 0.125, 0.250mmol/L). The stronger the inhibitory effect on cell proliferation (0.102¡À0.008, 0.083¡À0.007, 0.066¡À0.014, P<0.05), the synthesis and secretion of type I and III collagen were significantly reduced (P<0.05), p-ERK1/2 and p -AKT protein expression was significantly reduced (P<0.05). Conclusion Danshensu can negatively regulate the process of liver fibrosis by inhibiting PDGF-BB-induced HSC proliferation and activation, and at the same time inhibiting the phosphorylation of ERK and AKT proteins in the MAPK and PI3K pathways that are closely related to liver fibrosis. The mechanism may be related to Inhibition of ERK1/2 is related to the PI3K signal transduction pathway. For further information of this article and research, feel free to contact our team for asssitance. Original research was done by Mao Linlin, Dai Lili, Tang Jing
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