摘要
目的 观察磷脂酰肌醇3激酶特异性抑制剂（LY294002），对血小板源生长因子（PDGF-BB）促大鼠肝星状细胞（HSC）增殖与Ⅰ型胶原表达的影响，并探讨其作用机制。方法用不同浓度的PDGF-BB和LY294002对大鼠肝星状细胞株（HSC-T6）进行处理，MTT法检测细胞的增殖，逆转录聚合酶链反应方法（RT-PCR）检测HSC-T6内Ⅰ型胶原mRNA的表达。结果PDGF-BB在浓度1～10ng／ml时呈剂量依赖性地促进HSC细胞增殖（P〈0．05），当浓度大于10ng／ml时处理组间无显著差异（P〉0．05），其促增殖作用达到饱和。5μmol／L、10μmol／L、25μmol／L的LY294002均能显著且剂量依赖性地抑制PDGF-BB刺激的HSC-T6增殖（P〈0．001）。PDGF-BB能促进HSCI型胶原mRNA表达，24h、48h时相对于对照组的表达量为112．2％。182．5％。LY294002能显著抑制PDGF-BB促Ⅰ型胶原表达，24h、48h时相对表达量为76．4％，52．6％。结论磷脂酰肌醇3激酶信号途径是调节血小板源生长因子促肝星状细胞增殖与分泌胶原的重要通道，抑制该通路可以抑制肝星状细胞增殖和胶原表达，具有抗肝纤维化的作用，对防治肝纤维化有一定的意义。
Objective To investigate the effect of LY294002 on the proliferation and type Ⅰ collagen expression of rat hepatic stellate cells （HSCs） stimulated by platelet derived growth factor （PDGF） and explore its mechanism. Methods Rat HSCs stimulated by PDGF-BB were incubated with different concentrations of LY294002. Cell proliferation was assessed by MTT colorimetric assay. The mRNA of type Ⅰ collagen was examined by RT-PCR. Results PDGF significantly enabled to stimulate the proliferation of HSCS in a dose-dependent manner. The proliferation was dose-dependently in creased in PDGF with a dosage between 1.0 and 10 ng/ml. The proliferation effect of PDGF became saturated when the dosage was over 10 ng/ml. LY294002 （5,10,25 μmol/L） could significantly inhibit the proliferation of HSCs stimulated by PDGF in a dose-dependent manner. The expression of type Ⅰ collagen mRNA in HSCs treated by PDGF-BB was increased to accompany with intervention time elongation. LY294002 could down-regulate the expression of type Ⅰ collagen mRNA in HSCs treated by PDGF-BB. Conclusion The PI3K signal transduction pathway plays an important role in regulating the proliferation of HSCs stimulated by PDGF, and also regulates the expzession of the type Ⅰ collagen.
出处
《苏州大学学报（医学版）》
CAS
北大核心
2006年第3期389-391,411,共4页
Suzhou University Journal of Medical Science
关键词
磷脂酰肌醇3激酶
血小板源生长因子
肝星状细胞
LY294002
phosphatidylionsitol 3-kinase （PI3K）
platelet derived growth factor（PDGF）
hepatic stellate cell （HSC）
LY294002
