Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei, China.
J Med Food. 2012 Jun;15(6):557-62. doi: 10.1089/jmf.2011.1915. Epub 2012 Mar 9.
Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis, and inhibition of HSC activation may prevent liver fibrosis. Acetaldehyde, the most deleterious metabolite of alcohol, triggers HSC activation in alcoholic liver injury. In the present study, we investigated the protective effect of sodium ferulate (SF), a sodium salt of ferulic acid that is rich in fruits and vegetables, on acetaldehyde-stimulated HSC activation using precision-cut liver slices (PCLSs). Rat PCLSs were co-incubated with 350 μM acetaldehyde and different concentrations of SF. Hepatotoxicity was assessed by measuring enzyme leakage and malondialdehyde content in tissue. α-Smooth muscle actin, transforming growth factor-β(1), and hydroxyproline were determined to assess the activation of HSCs. In addition, matrix metalloproteinase (MMP)-1 and the tissue inhibitor of metalloproteinase (TIMP-1) were determined to evaluate collagen degradation. SF prominently prevented the enzyme leakage in acetaldehyde-treated slices and also inhibited HSC activation and collagen production stimulated by acetaldehyde. In addition, SF increased MMP-1 expression and decreased TIMP-1 expression. These results showed that SF protected PCLSs from acetaldehyde-stimulated HSC activation and liver injury, which may be associated with the attenuation of oxidative injury and acceleration of collagen degradation.
活化的肝星状细胞(HSCs)在肝纤维化中起关键作用,抑制 HSC 活化可能预防肝纤维化。乙醛是酒精最具危害性的代谢物,可引发酒精性肝损伤中的 HSC 活化。在本研究中,我们使用精密切割肝切片(PCLS)研究了富含水果和蔬菜的阿魏酸钠(SF)对乙醛刺激的 HSC 活化的保护作用。将大鼠 PCLS 与 350μM 乙醛和不同浓度的 SF 共同孵育。通过测量组织中酶漏出和丙二醛含量来评估肝毒性。α-平滑肌肌动蛋白、转化生长因子-β(1)和羟脯氨酸用于评估 HSCs 的活化。此外,基质金属蛋白酶(MMP)-1 和金属蛋白酶组织抑制剂(TIMP)-1用于评估胶原降解。SF 显著防止了乙醛处理的切片中的酶漏出,并且还抑制了乙醛刺激的 HSC 活化和胶原产生。此外,SF 增加了 MMP-1 的表达并降低了 TIMP-1 的表达。这些结果表明,SF 可保护 PCLS 免受乙醛刺激的 HSC 活化和肝损伤,这可能与氧化损伤的减轻和胶原降解的加速有关。