毛蕊花糖苷对血小板衍生生长因子BB处理后大鼠肝星状细胞的影响

doi:10.3969/j.issn.1004-616x.2018.06.011

Abstract

Abstract: OBJECTIVE: To investigate effect of verbascoside on recombinant platelet-derived growth factor (rrPDGF)-BB-mediated migration,collagen deposition and fibrosis in rat hepatic stellate cells (HSC). METHODS: HSC cell cultures were divided into:rrPDGF-BB+ verbascoside (1.5,3,6 mg/L) group[recombinant rat PDGF-BB (rrPDGF-BB) pretreatment for 24 h,no verbascoside intervention],rrPDGF-BB group (rrPDGF-BB pretreatment for 24 h,no verbascoside intervention),control group (no rrPDGF-BB pretreatment,no verbascoside intervention). Scratch test was used to detect cell migration ability,ELISA was used to detect content of type I collagen (Col-I),Western blot was used to detect fibrotic HSC activation marker α-SMA protein and apoptosis effector molecule caspase-3,and expression level of ERK1/2 and Akt signaling pathway-related proteins. RESULTS: Compared with the control group,rrPDGF-BB group promoted the migration of HSC (P < 0.01),verbascoside (1.5,3.0,6.0 mg/L) group significantly inhibited the migration of HSC (P < 0.01). Moreover,inhibition of HSC migration by verbascoside was dose-dependent (r=0.894,P=0.038). With increasing test substance concentrations,Col-I secretion showed a decreasing trend. Among them,the effect of inhibiting collagen production was the most obvious in the 6 mg/L verbascoside group (P < 0.01). Verbascoside (1.5,3.0,6.0 mg/L) inhibited expression of α-SMA protein,activated activities of caspase-3,and significantly reduced expression of ERK1/2,P-ERK1/2,Akt and P-Akt proteins. Moreover, expression of the determination protein was also shown to have a dose-effect relationship among the various dose groups of verbascoside (0.826 < r < 0.997,P < 0.01). CONCLUSION: Verbascoside inhibited the activation,migration and fibrosis of HSC which was mediated by rrPDGF-BB. The evidence suggests that activation of caspase-3 by verbascoside blocked ERK1/2 and the Akt signaling pathway,and inhibited ECM excessive deposition and collagen formation in HSC.

Key words: verbascoside, hepatic stellate cells, hepatic fibrosis, activation

CLC Number:

R735.7

YOU Shuping, ZHANG Shilei, ZHAO Jun, MA Long, LIU Tao. Effect of verbascoside on platelet derived growth factor-BB-mediated activities in rat hepatic stellate cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(6): 473-478.

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Effect of verbascoside on platelet derived growth factor-BB-mediated activities in rat hepatic stellate cells

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