安徽医科大学学报Issue(3)：319-323,5.
姜黄素对大鼠肝星状细胞中TGF-β调节的NADPH氧化酶4的激活及Smad信号通路的影响
Curcumin attenuates hepatic fibrogenesis through interrupting TGF-β-mediated NADPH oxidase 4 activation and Smad signaling in vitro
摘要
Abstract
Objective To observe the effects of curcumin on activation and proliferation of hepatic stellate cells (HSCs) and, their expression of NADPH oxidase 4 (NOX 4) and smad signaling factors of rat hepatic stellate cells line in vitro using a rat HSC line. Methods Synchronized HSC-T6 cells were treated with different dose of purified curcumin (0, 5, 10, 20, 40μmol/L). Untreated cells were viewed as controls. MTT technique analysis was used to examine the proliferation of the hepatic stellate cells stimulated by differernt concentration of curcumin;the mR-NA expression ofα-smooth muscle actin (α-SMA) and main constituents in extracellular matrix I procollagen (α1I collagen) were determined by RT-PCR in TGF-β-stimulated HSCs, and the antifibrotic effects on the protein ex-pression of α-SMA, α1I collagen, NADPH oxidase (NOX) protein (NOX 4) and the phosphorylation level of smad 2 and smad 3 was assessd by western blot;beta-actin (β-actin) was detected as the normalization control in the hepatic smllate cells was examined by Western blot analysis. Results The inhibition rate of HSC-T6 cells was the largest with curcumin for 48 h, significantly lower than that of TGF-β-stimulated group, 5 μmol/L, 10 μmol/L and 20 μmol/L group (P<0. 05). Notably, curcumin could obviously reduce the expression ofα-SMA andα1I collagen at both mRNA and protein levels and reduce the deposition of extracellular matrix. Treatment of curcumin markedly blocks up-regulation of NOX4 by TGF-β. It also significantly reduced TGF-β-induced Smad 2/3 phos-phorylation, and this effect observed dose-dependent. Conclusion Curcumin inhibited TGF-β-mediated HSC acti-vation in vitro, which was involved in Smad signaling pathway, and consequently influenced the profibrotic actions of TGF-β on HSC-T6 cells. Our results suggest that curcumin could become potential candidate for the therapeutic applications by inhibiting the TGF-β induced NOX activation and Smad signaling.关键词
姜黄素/大鼠肝星状细胞/转化生长因子β/NADPH氧化酶4/Smad蛋白Key words
curcumin/rat hepatic stellate cell/transforming growth factor-β/NADPH oxidase 4/drosophila mothers against decapentaplegic protein分类
医药卫生引用本文复制引用
王雅蕊,李俊,黄成,李小枫,李晓慧,王欢..姜黄素对大鼠肝星状细胞中TGF-β调节的NADPH氧化酶4的激活及Smad信号通路的影响[J].安徽医科大学学报,2015,(3):319-323,5.基金项目
国家自然科学基金(编号:81273526) （编号:81273526）
