Shimizu I, Mizobuchi Y, Yasuda M, Shiba M, Ma Y R, Horie T, Liu F, Ito S
Second Department of Internal Medicine, School of Medicine, University of Tokushima, Tokushima, Japan.
Gut. 1999 Jan;44(1):127-36. doi: 10.1136/gut.44.1.127.
Hepatic stellate cells play a key role in the pathogenesis of hepatic fibrosis.
To examine the inhibitory effect of oestradiol on stellate cell activation.
In vivo, hepatic fibrosis was induced in rats by dimethylnitrosamine or pig serum. In vitro, rat stellate cells were activated by contact with plastic dishes resulting in their transformation into myofibroblast-like cells.
In the dimethylnitrosamine and pig serum models, treatment with oestradiol at gestation related doses resulted in a dose dependent suppression of hepatic fibrosis with restored content of hepatic retinyl palmitate, reduced collagen content, lower areas of stellate cells which express alpha smooth muscle actin (alpha-SMA) and desmin, and lower procollagen type I and III mRNA levels in the liver. In cultured stellate cells, oestradiol inhibited type I collagen production, alpha-SMA expression, and cell proliferation. These findings suggest that oestradiol is a potent inhibitor of stellate cell transformation.
The antifibrogenic role of oestradiol in the liver may contribute to the sex associated differences in the progression from hepatic fibrosis to cirrhosis
肝星状细胞在肝纤维化的发病机制中起关键作用。
研究雌二醇对星状细胞激活的抑制作用。
在体内，用二甲基亚硝胺或猪血清诱导大鼠肝纤维化。在体外，大鼠星状细胞通过与塑料培养皿接触而被激活，从而转化为肌成纤维细胞样细胞。
在二甲基亚硝胺和猪血清模型中，以与妊娠相关的剂量给予雌二醇治疗，可导致肝纤维化呈剂量依赖性抑制，肝视黄醇棕榈酸酯含量恢复，胶原含量降低，表达α平滑肌肌动蛋白（α-SMA）和结蛋白的星状细胞面积减小，肝中I型和III型前胶原mRNA水平降低。在培养的星状细胞中，雌二醇抑制I型胶原产生、α-SMA表达和细胞增殖。这些发现表明雌二醇是星状细胞转化的有效抑制剂。
雌二醇在肝脏中的抗纤维化作用可能导致肝纤维化发展为肝硬化过程中的性别相关差异
