Matsui Hiroko, Ikeda Kazuo, Nakajima Yuji, Horikawa Saburo, Imanishi Yukihiro, Kawada Norifumi
Department of Anatomy, Graduate School of Medicine, Osaka City University, Osaka, Japan.
J Hepatol. 2004 Jun;40(6):917-25. doi: 10.1016/j.jhep.2004.02.011.
BACKGROUND/AIMS: We tested the pharmacological action of sulfur-containing amino acids on the development of liver fibrosis in rats and on the function of cultured stellate cells.
Liver fibrosis was induced in rats by thioacetamide administration or by ligating the common bile duct. DNA synthesis of cultured stellate cells was evaluated by BrdU incorporation. The expression of proteins and phospho-proteins was determined by western blot analysis. mRNA expression was evaluated by RT-PCR.
Oral administration of l-cysteine or l-methionine attenuated the deposition of collagen in liver tissues in the two fibrotic models, accompanying a reduction in the expression of smooth muscle alpha-actin and platelet-derived growth factor receptor beta and mRNAs of collagens, transforming growth factor-betas and tissue inhibitors of matrix metalloproteinase. In cultured stellate cells, l-cysteine and l-methionine suppressed the DNA synthesis and the expression of growth factor receptors, smooth muscle alpha-actin and type I collagen. They hampered the phosphorylation of p44/42 MAPK and Akt under platelet-derived growth factor-BB stimulation. Stellate cells were found to express methionine adenosyltransferase 2A.
l-Cysteine and l-methionine regulate the activation of stellate cells. Their oral supply aids the suppression of the progression of liver fibrosis.
背景/目的：我们测试了含硫氨基酸对大鼠肝纤维化发展及培养的星状细胞功能的药理作用。
通过给予硫代乙酰胺或结扎胆总管诱导大鼠肝纤维化。通过掺入BrdU评估培养的星状细胞的DNA合成。通过蛋白质印迹分析确定蛋白质和磷酸化蛋白质的表达。通过RT-PCR评估mRNA表达。
在两种纤维化模型中，口服L-半胱氨酸或L-蛋氨酸可减轻肝组织中胶原蛋白的沉积，同时平滑肌α-肌动蛋白、血小板衍生生长因子受体β以及胶原蛋白、转化生长因子-β和基质金属蛋白酶组织抑制剂的mRNA表达降低。在培养的星状细胞中，L-半胱氨酸和L-蛋氨酸抑制DNA合成以及生长因子受体、平滑肌α-肌动蛋白和I型胶原蛋白的表达。在血小板衍生生长因子-BB刺激下，它们阻碍p44/42 MAPK和Akt的磷酸化。发现星状细胞表达蛋氨酸腺苷转移酶2A。
L-半胱氨酸和L-蛋氨酸调节星状细胞的活化。口服补充它们有助于抑制肝纤维化的进展。
