丹参素对转化生长因子β1刺激肝星状细胞信号传导的影响

Effects of Danshensu on TGF β1 stimulated hepatic stellate cell signal transduction

目的:探讨丹参素对转化生长因子β1(Transformation growth factor,TGFβ1)刺激大鼠肝星状细胞(Hepatic stellate cell,HSC)信号传导通路的影响。方法:体外分离、培养大鼠肝HSC,检测丹参素(0.0625～0.2500mmol/L)对TGFβ1促进HSC活化、HSC表达α-SMA和HSC表达Smad2、Smad3、Smad7mRNA的影响。结果:丹参素(0.0625～0.2500mmol/L)对TGFβ1引起的HSC增殖具有明显的抑制作用,并呈剂量依赖性(P<0.05)。0.25mmol/L丹参素对HSC作用48小时能下调α-SMA的表达(P<0.05),也能下调TGFβ1诱导的HSCα-SMA表达(P<0.05),从而抑制HSC活化。TGFβ1促进HSC中Smad2、3、7 mRNA的表达;丹参素能下调TGFβ1诱导的HSC中Smad2、Smad3 mRNA的表达并能上调Smad7 mRNA表达(P<0.05)。结论:丹参素能上调HSC中Smad7mRNA表达,并下调Smad2、Smad3 mRNA表达,恢复正常的TGFβ1跨膜信号转导,抑制HSC活化和TGFβ1促进HSC活化的作用。

Objective：To investigate the role of Danshensu on TGF β 1 stimulated signal transduction in rat hepatic stellate cells （HSCs）. Methods：The mice HSCs were isolated and cultured for the following study.HSC were treated with different concentration Danshensu （0.062 5 ~ 0.250 0 mmol/L）and TGF β1 to detect the proliferation, α -SMA protein expression and the chang of Smad2, Smad3, Smad7 mRNA. Results： （ 1 ）Danshensu in the concentration of 0.062 5 - 0.250 0 mmol/L could prevent the proliferation of HSC induced by TGF β 1 in a dose-dependent manner （P〈0.05）. （2）The concentration of 0.250 0 mmol/L Danshensu could downregulate α -SMA protein expression at 48th hour in HSC, with or without stimulation of TGFβ 1 （P〈0.01）, and the activation of HSC was inhibited also. （3）TGF β1 increased the mRNA level of Smad2,3,7 in HSC;Danshensu could downregnlate the mRNA level of Smad2,3 and upregulate the mRNA level of Smad7 in HSC induced by TGFβ1 （P〈0.01）.Conclusion： Danshensu could restore the normal transmembrane signal of TGF β1 through upregulation of Smad7 mRNA expression and downregulation of Smad2, Smad3 mRNA expression in HSC.