首页> 中文期刊> 《实用医学杂志》 >血管紧张素Ⅱ靶向调控血小板源性生长因子信号通路促进肝纤维化的形成

血管紧张素Ⅱ靶向调控血小板源性生长因子信号通路促进肝纤维化的形成

         

摘要

目的:探讨血管紧张素Ⅱ(AngⅡ)对肝星状细胞(HSC)合成胶原的影响及其机制。方法:以不同浓度的AngⅡ刺激大鼠HSC,采用[3H]-脯氨酸(3H-pro)掺入释放法检测胶原合成的情况, RT-PCR检测Ⅰ、Ⅲ型前胶原mRNA的表达,原位杂交及免疫组化的方法分别检测血小板源性生长因子β受体(PDGFR-β)的表达。结果:10-8~10-5 mol/L AngⅡ能剂量依赖性促进HSC对3H-pro的掺入率(P<0.05),促进胶原的合成,但10-6 mol/L AngⅡ作用最强。与培养激活的大鼠HSC相比,加入10-6 mol/L AngⅡ刺激后,Ⅰ、Ⅲ型前胶原mRNA的表达明显增加。免疫组化结果显示,培养激活的大鼠HSC可表达少量的PDGFR-β蛋白,但与正常对照组相比10-6 mol/L AngⅡ刺激后表达明显增强(P <0.01)。细胞原位杂交结果显示10-6 mol/L AngⅡ刺激HSC后表达 PDGFR-β mRNA明显增加(P <0.01)。结论:AngⅡ可促进 HSC 胶原的合成, PDGF 信号通路可能在其中起着重要的作用。%Objective To investigate the effect and mechanism of AngⅡ on collagen in hepatic stellate cell. Methods HSCs were isolated and cultured, 3H-pro incorporation method was used to evaluate the effects of different doses of AngⅡ on the proline syntheses. RT-PCR assay were used to assess changes in mRNA expression levels of type Ⅰ and Ⅲ procollagen. PDGFR-β mRNA and protein were determined by in situ hybridization and immunocytochemistry. Results 10-8~ 10-5 mol/L AngⅡ could significantly increase the 3H-pro incorporation rate of HSC in a dose-dependent style, 10-6 mol/L AngⅡis the most effective dose. The cultured HSC showed a little expression of type Ⅰ and Ⅲ procollagen mRNAs, while 10-6 mol/L AngⅡwas able to enhance the expression for type Ⅰ and Ⅲ procollagen mRNAs significantly(P < 0.01). AngⅡalso could enhance both mRNA and protein expression of PDGFR-β on HSC(P < 0.01). Conclusion These results suggest that AngⅡ could promote HSC collagen synthesis by enhancing the expressions of PDGFR-β.

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