β-雌二醇纳米粒抗肝纤维化的效果及对TGF—β1和CTGF的影响  

The effect of anti-fibrosis and suppression of TGF-β1 and CTGF by β-estradiol nanopartide and β-estradiol in hepatic fibrosis rats

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

机构地区：[1]中南大学湘雅医院感染病科,湖南长沙410008

出　　处：《中国医师杂志》2008年第11期1466-1469,共4页Journal of Chinese Physician

基　　金：湖南省自然科学基金资助项目（03GGY3060）

摘　　要：目的研究自行制备的肝靶向聚氰基丙烯酸正丁酯β-雌二醇纳米粒（E2-PBCA—NP）抗肝纤维化的效果，以及对猪血清诱导的肝纤维化动物模型肝脏TGF—β1、CTGF表达的影响。方法将SD大鼠随机分成5组，除正常对照外，其余4组均腹腔注射猪血清（0．5ml／次，2次／周）构建大鼠免疫性肝纤维化模型。β-雌二醇治疗组、β雌二醇纳米粒治疗组、空白纳米粒组在第9周给予腹腔注射干预药物，2次／周；在12周末处死老鼠，Masson染色观察肝脏纤维化改变，RT—PCR检测肝组织中TGF-β1和CTGFmRNA的含量，免疫组化观察TGF-β1及CTGF蛋白的表达。结果与模型组比较，β-雌二醇纳米粒和β-雌二醇治疗组均能显著逆转猪血清诱导的肝纤维化，肝纤维化分期好转（P〈0．05）；β-雌二醇纳米粒治疗组与β-雌二醇治疗组2组比较差异有统计学意义（P〈0．05）；β-雌二醇纳米粒治疗组与β-雌二醇治疗组肝组织TGF—β1、CTGFmRNA和蛋白的表达下降（P〈0．01），但β-雌二醇和β-雌二醇纳米粒治疗组之间比较差异无统计学意义（P〉0．05）。结论纳米化后的β-雌二醇仍具有抗肝纤维的作用，与无纳米化β-雌二醇比较，抗肝纤维的作用更强。β-雌二醇纳米粒能够抑制TGF—β1及其下游信号CTGF的表达。Objective To investigate the possibility of anti-liver fibrosis of β-estradiol nanoparticle prepared by interracial polymerization method with butyleyanoacylate as carrier material （ E2-PBCA-NP） and its effect on the expression of transforming growth factor β1 and connective tissue growth factor in pig serum induced animal fibrotic model. Methods Male Sprague-Dawley （SD） rats were random divided into five groups. Except normal control group, other four groups were all given intraperitoneal injection with pig serum. Therapeutic drugs were administered to rats from the ninth week after injection of pig serum. All rats were killed at the end of the twelfth week. Several experiments were clone as below, the tissues of liver were obseIved by Masson staining, and the mRNA of TGF-β1 and CTGF of liver samples were detected by RT-PCR. Meanwhile, the expression of TGF-β1 and CTGF protein were detected by immunohistochemistry. Results It showed that both E2 and E2-PBCA-NP treatment groups had lower stage of liver fibrosis, according to the observation of pathology by Masson staining （ P 〈 0. 05 ）. The anti-liver fibrosis effect of E2-PBCA-NP treatment group was better than that of E2 treatment group （ P 〈 0. 05 ）. The mRNA and protein level of TGF-β1 and CTGF were markedly reduced by E2 and E2-PBCA-NP treatment, compared with liver fibrotic model groups （ P 〈 0. 01 ）. There was no statistical difference between E2-PBCA-NP and E2 treatment （ P 〉 0. 05 ）, while no significant change was observed in blank nano - particle group （ P 〉 0. 05 ）. Conclusion Both E2-PBCA-NP and E2 had anti-liver fibrosis activity. E2-PBCA-NP has stronger anti - liver fibrosis activity than E2, which could be resulted from the inhibition of TGF-β1 and CTGF expression.

关 键 词：雌二醇 药理学 肝硬化 转化生长因子Β 胞间信号肽类和蛋白质类 纳米结构 

分 类 号：R96[医药卫生—药理学]