β-雌二醇及其纳米粒对肝星状细胞TGF-β1和CTGF的影响  

The effect of TGF-β1 and CTGF treated with β-estradiol nanoparticle and β-estradiol on activated rat hepatic stellate cells

作　　者：刘菲[1] 谢建萍[1] 黄柳云[1] 周建亮[1] 谭德明[1] 潘一峰[2] 

机构地区：[1]中南大学湘雅医院感染病科,湖南长沙410008 [2]卫生部纳米生物技术重点实验室

出　　处：《胃肠病学和肝病学杂志》2007年第6期561-565,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：湖南省自然科学基金(03GGY3060)

摘　　要：目的本研究首先观察纳米化后的β-雌二醇纳米粒是否和普通β-雌二醇一样对HSC增殖仍具有抑制作用;再比较β-雌二醇和β-雌二醇纳米粒对TGF-β1和其下游信号CTGF mRNA和蛋白表达的影响;进一步探讨β-雌二醇和β-雌二醇纳米粒抗肝纤维化的机制。方法①用不同浓度的β-雌二醇、β-雌二醇纳米粒干预HSCs,噻唑蓝(MTT)法检测不同时间点β-雌二醇、β-雌二醇纳米粒对HSCs增殖的影响。②用逆转录-聚合酶链式反应(RT-PCR)方法检测分析其对HSCs的TGF-β1、CTGF的mRNA表达的影响。③用免疫细胞化学方法分析其对HSCs的TGF-β1、CTGF蛋白的表达的影响。结果MTT法发现β-雌二醇、β雌二醇纳米粒都能抑制HSCs的增殖,下调HSCs TGF-β1 mRNA、CTGF mRNA的表达,减少HSCs TGF-β1、CTGF蛋白表达量,且β-雌二醇纳米粒作用更强。结论β-雌二醇纳米粒和β-雌二醇一样具有抑制HSC增殖的作用,其抗肝纤维化的机制可能是通过抑制TGF-β1及其下游信号CTGF的mRNA和蛋白表达有关。Objective To observe whether β-estradiol nanoparticle has the same suppressive effects on HSCs proliferation as β-estradiol, and then compare their effect on the expression of mRNA and protein of TGF-β1and its downstream signaling CTGF. The anti-fibrotic mechanism of β-estradiol and β-estradiol nanoparticles is further investigated. Methods Hepatic stellate ceils were treated with different concentration of β-estradiol and β-estradiol nanoparticle, then their effects on the proliferation of HSCs were detected by MTT. Hepatic stellate ceils were treated with 10^-8mol/L of β-estoadiol or β-estoadiol nanoparticle for 48 h, detected by RT-PCR, then expression of TGF-β1 and CTGF mRNA and protein in hepatic stellate ceils were detected by RT-PCR or Immunocytochemistry. Results The suppressive effect of β-estradiol and β-estradiol nanoparticle on the proliferation of activated HSCs were confirmed . We found that β-estradiol and β-estradiol nanoparticle down-regulate the expression of TGF-β1 and CTGF mRNA and protein. There was significant of difference between the effect of β-estradiol and β-estradiol nanoparticle. β-estradiol nanoparticle had better effect than β-estradiol. Conclusion Both β-estradiol nanoparticle and β-estradiol have anti-fibrosis function. The antifibrosis mechanisms of β-estradiol nanoparticle and β-estradiol may be result from the following factors： inhibiting the proliferation of HSCs, suppressing the expression of pro-fibrogenic cytokine TGF-β1 and it＇s downstream signaling CTGF which play an essential role in the process of hepatic fibrosis.

关 键 词：雌二醇 雌二醇纳米粒 肝星状细胞 转化生长因子Β1 结缔组织生长因子 

分 类 号：R575[医药卫生—消化系统]