关键词: 普萘洛尔, 肝星状细胞, 肝硬化

Abstract: Objective To explore the inhibitory effect of propranolol on hepatic stellate cells (HSCs) activation in vitro via PDGFR/Akt pathway. Methods HSCs were studied as an in vitro model. The cells were divided into control group, saline group, and treatment groups A, B, and C. Cells in the control group was cultured under normal condition without special intervention. Cells in the saline group was treated with physiological saline vehicle. Cells in the three treatment groups A, B and C were treated with different concentrations of propranolol (10 μmol/L, 50 μmol/L, 100 μmol/L, respectively) for 24 h. The cells were then collected, and the morphological changes of each group were observed. The proliferation and apoptosis of HSCs were investigated. The protein concentration of types I and III collagen, MMP-2 and TNF-α, vascular endothelial growth factor (VEGF) and platelet-derived factor (PDGF) in different groups of cells were compared. Results (1) The morphology of HSCs in the control group and the saline group did not change significantly, whereas the cells in the propranolol treated A, B and C groups showed decreased cell density, poor adherence, and enhanced cell-to-cell connection. The changes were more obvious with the increase of propranolol concentration. (2) there was no significant change in the cells proliferation and apoptosis between the saline group and the control group (P>0.05), and the proliferation of cells in the treatment groups A, B and C dose-dependently decreased. The increase of apoptosis was significantly different from that of the control group (P<0.05). (3) The concentrations of types I and III collagen were not significantly different between the cells in the saline group when compared with the control group (P>0.05), whereas the concentrations of types I and III collagen in A, B and C groups were dose dependently lower than those in the control group (P<0.05). (4) There was no significant difference in MMP-2 and TNF-α levels between the saline group and the control group (P>0.05), whereas the levels of MMP-2 and TNF-α in A, B and C groups were dose-dependently lower than the control group (P<0.05). (5) The levels of VEGF and PDGF in the saline group were not significantly different from the control group (P>0.05). The levels of VEGF and PDGF in A, B and C groups were dose-dependently decreased when compared with the control group (P<0.05). Conclusion Propranolol inhibits the proliferation of HSCs and promote the cells apoptosis. It also reduces the expression of types I and III collagen in HSCs, which may have great significance in delaying the progression of liver cirrhosis.

Key words: Propranolol, Hepatic stellate cells, Cirrhosis