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甘草酸对转化生长因子β1刺激肝星状细胞信号传导的作用 被引量:11

Effects of giycyrrhizin on TGF β1 stimulated hepatic stellate cell signaling transduction
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摘要 目的探讨甘草酸对转化生长因子β1(TGF β1)刺激大鼠肝星状细胞(HSC)胞内信号传导通路的作用。方法体外分离、培养大鼠肝HSC,甘草酸与TGFβ1刺激的HSC共同孵育。逆转录聚合酶链反应法检测1-1000 μmol/L甘草酸对TGF β1刺激的HSC中Smad2、3、7 mRNA的表达;Western印迹法检测1-1000μmol/L甘草酸对TGF β1刺激的HSC中Smad2、3、7蛋白及Ⅰ、Ⅲ型胶原蛋白的表达水平。结果TGFβ1促进HSC中Smad2、3、7 mRNA及蛋白的表达,同时促进Ⅰ、Ⅲ型胶原蛋白的表达。1-1000μmol/L甘草酸抑制Smad2、3、7 mRNA及蛋白的表达,并且抑制Ⅰ、Ⅲ型胶原蛋白的表达,均呈剂量依赖性。结论甘草酸可能通过干预大鼠HSC中TGFβ信号通路而减少胶原合成和发挥抗纤维化作用。 Objective To investigate the role of glycyrrhizin on TGF β 1 stimulated signaling transduction in rat hepatic stellate cells (HSCs). Methods The mice HSCs were isolated and cultured with or without glycyrrhizin ( 1 μmol/L - 1 000 μmol/L) in vitro after TGFβ 1 stimulation. The mRNA level of Smad2, 3. 7 were measured with RT-PCR; protein expression level of Smad2, 3. 7 and collagen I , Ⅲ were analyzed with Western blot. Results TGF β 1 increased the mRNA level and protein expression of Smad2, 3, 7 in HSC; it also increased protein expression of collagen I and Ⅲ. 1 μ mol/L -1000 μ mol/L glycyrrhizin decreased the mRNA level and protein expression of Smad2,3,7; it also inhibited protein expression of collagen I and III gradually. Conclusion Interventing the TGF signaling pathway and decreasing the synthesis of collagen, might be involved in the anti-fibrosis mechanism of glycyrrhizin.
出处 《中华肝脏病杂志》 CAS CSCD 北大核心 2005年第11期828-831,共4页 Chinese Journal of Hepatology
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参考文献9

  • 1Wang JY, Guo JS, Li H, et al. Inhibitory effect of glycyrrhizin on NF-kappaB binding activity in CCl4- plus ethanol-induced liver cirrhosis in rats. Liver, 1998, 18: 180-185.
  • 2蔡瑜,沈锡中,王吉耀.甘草酸对大鼠肝纤维化过程中肝组织基因表达的影响[J].中华医学杂志,2003,83(13):1122-1125. 被引量:34
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二级参考文献9

  • 1Wang JY, Guo JS, Li H,et al. Inhibitory effect of glycyrrhizin on NF-κB binding activity in CCl4-plus ethanol-induced liver cirrhosis in rats. Liver, 1998,18:180-185.
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  • 6Lin X, Liang M, Feng XH, et al. Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of smad2 in transforming growth factor-β signaling. J Biol Chem.2000,275:36818-36822.
  • 7Bonni S, Wang HR, Causing CG, et al .TGF-β induces assembly of a smad2-smurf2 ubiquitin ligase complex that targets snoN for degradation. Nat Cell Biol, 2001,3:587-595.
  • 8Kavsak P, Rasmussen RK, Causing CG, et al. Smad7 binds to smurf2 to form an E3 ubiquitin ligase that targets the TGF-β receptor for degradation. Mol Cell ,2000,6:1365-1375.
  • 9Zhang Y, Chang C, Gehling DJ et al. Regulation of smad degradation and activity by smurf2, an E3 ubiquitin ligase. Proc Natl Acad Sci USA, 2001,98:974-979.

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