17β-雌二醇及代谢产物对大鼠肝星状细胞功能的影响  

The effect of 17β-estradiol and its metabolites on hepatic stellate cells in rats

作　　者：刘清华[1] 李定国[1] 宗春华[1] 黄新[1] 徐芹芳[1] 陆汉明[1] 

机构地区：[1]上海第二医科大学附属新华医院消化科,200092

出　　处：《中华消化杂志》2004年第4期226-229,共4页Chinese Journal of Digestion

摘　　要：目的　探讨 17β 雌二醇 (β Est)及其主要代谢产物 2 羟雌二醇 (2OHE)、2 甲氧雌二醇(2MeOE)对肝星状细胞 (HSC)功能的影响及其可能的作用途径。方法　采用原位酶灌注法和密度梯度离心法分离HSC。初次传代后 ,HSC随机分成 10组 ,分别加入不同浓度 β Est、2OHE、2MeOE ,加药后72h ,采用MTT、ELISA及免疫组化法分别检测HSC增殖、培养液中透明质酸 (HA)和Ⅳ型胶原 (CⅣ )含量及细胞中α 平滑肌肌动蛋白 (α SMA)、雌激素受体 (ER)表达。结果　在 10 -9～ 10 -7mol/L浓度范围内 ,β Est、2OHE、2MeOE能抑制活化HSC增殖、分泌细胞外基质 (ECM ) ,呈剂量依赖关系 ,10 -7mol/Lβ Est、2OHE、2MeOE能抑制活化HSC表达α SMA ,生物学活性依次为 2MeOE >2OHE >β Est。 10 -7mol/Lβ Est能促进HSC表达ERβ蛋白 ,而相同浓度 2OHE、2MeOE对HSC表达ERβ蛋白无影响。 结论　在生理条件下 ,雌激素抑制肝纤维化形成可能通过其代谢产物发挥作用。Objective To evaluate the effect of 17β-estradiol(β-Est) and its metabolites on function of hepatic stellate cells (HSCs). Methods HSCs were isolated from the liver of Sprague-Dawley rats by pronase-collagenase perfusion and density gradient centrifugation. The passaged HSCs were randomly divided into 10 groups and different concentrations of β-Est,2-hydroxyestradiol (2OHE) or 2-methoxyestradiol (2MeOE) were added to the cell groups separately. After 72 hours incubation,the degree of cell proliferation,hyahuronicacid and type Ⅳ collogen secretion,α-smooth muscle actin (α-SMA) and estrogen receptor (ER) expression were determined by MTT assay,ELISA or immunohistochemistry,respectively. Results β-Est and its metabolites inhibited HSCs proliferation and ECM secretion in concentration-dependenty manner(10 -9 -10 -7 mol/L). α-SMA expression was inhibited by β-Est and its metabolites at the concentration of 10 -7 mol/L,the order of potency being 2MeOE>2OHE>β-Est. Besides,β-Est could promote the expression of ER β by HSC at the concentration of 10 -7 mol/L but not its metabolites. Conclusion The present results indicate that β-Est may attenuate hepatic fibrosis and the possible mechanism is via the action of its metabolites.

关 键 词：17Β-雌二醇 代谢产物 大鼠 肝星状细胞功能 肝纤维化 生物学活性 

分 类 号：R575.2[医药卫生—消化系统]