摘要
目的比较β-雌二醇纳米化前、后对猪血清诱导的肝纤维化动物模型肝脏纤维化的疗效及雌二醇抗肝纤维化的机制。方法将S-D大鼠随机分为健康对照组、模型对照组、雌二醇治疗组、雌二醇纳米粒组和空白纳米粒组，每组10只，除健康对照组外，其余4组均腹腔注射猪血清（0．5mL／次，2次／周）。雌二醇治疗组、雌二醇纳米粒组和空白纳米粒组在第9周给予腹腔注射相应的干预药物，每周2次；在12周末处死大鼠。免疫组织化学法检测平滑肌肌动蛋白（α—SMA）的表达；比色法检测一氧化氮合酶（NOS）、一氧化氮（NO）、总抗氧化能力（T—AOC）和谷胱甘肽（GSH）；RT—PCR检测肝组织Ⅰ、Ⅲ型胶原、结缔组织生长因子（CTGF）、转化生长因子-β1（TGF-β1）及基质金属酶（MMP-1）、组织金属蛋白酶抑制剂（TIMP-1）mRNA的表达。结果肝纤维化动物模型肝脏组织的Ⅰ、Ⅲ型胶原、TGF-β1、CTGF和TIMP-1mRNA的表达在雌二醇纳米粒治疗组和雌二醇治疗组均有明显减少，MMP-1mRNA的表达明显增多，与模型对照组、空白纳米粒组比较，差异有统计学意义（P〈0．05）；经治疗后雌二醇治疗组和雌二醇纳米粒组的T—AOC、NO、NOS、GSH活性均有提高，与模型对照组、空白纳米粒组比较，差异有统计学意义（P〈0．05）；但雌二醇治疗组和雌二醇纳米粒组比较，差异无统计学意义（P〉O．05）。结论：雌二醇通过抗氧化、降低Ⅰ、Ⅲ型胶原产生，抑制与肝纤维化有关的细胞因子TGF-β1及其下游信号CTGF的表达，促进MMP-1表达但抑制TIMP-1的表达等发挥其抗肝纤维化作用。纳米化β-雌二醇的抗大鼠免疫性肝纤维化作用比无纳米化β-雌二醇更强。
Objective To investigate the anti-liver fibrosis effects of nanometer drug estradiol poly-butylcyanoacrylate nanoparticles （E2-PBCA-NP） on pig serum-induced animal liver fibrosis models and to study the underlying anti-fibrosis mechanisms. Methods Sprague-Dawley （S-D） rats were divided randomly into five groups： normal control group, estradiol treatment group, model control group, E2-PBCA-NP treatment group and blank nanoparticles treatment group. Except normal control rats, the rats in other groups were all given pig serum by intraperitoneal injection. The corresponding intervention drugs were administered to rats at the ninth week after the first administration of pig serum. All rats were sacrificed at the end of the twelfth week. The expression of α-smooth muscle actin （α-SMA） protein was determined by immunohistochemistry. The levels of total antioxidation capacity （T-AOC）, nitric oxide （NO）, nitric oxide synthase （NOS） and glutathione （GSH） in serum and liver tissues were determined by colorimetry. The mRNA levels of collagen type Ⅰ and Ⅲ, transforming growth factor（TGF）-β1, connective tissue factor（CTGF）, matrix metallo- proteinase（MMP）-1 and tissue inhibitor of metalloproteinases （TIMP）-1 were detected in liver samples by reverse transcription-polyrnerase chain reaction （RT-PCR）. Results According to RT-PCR analysis, the mRNA expressions of collagen typeⅠ and Ⅲ, TGF-β1, CTGF and TIMP-1 were markedly reduced and the mRNA expression of MMP-1 was increased in E2 treated group and E2-PBCA-NP treated group as compared with liver fibrotic model and blank nanoparticles groups （P 〈 0.05）. The levels of T-AOC, NO, NOS, GSH in liver almost turned to normal in E2 and E2-PBCA-NP treated groups, as compared with those in the liver fibrotic model and blank nanoparticles groups （P 〈 0.05）. There were no significant differences between E2-PBCA-NP treated group and E2 treated group （P 〉 0.05）. Conclusions Estradiol can block the progression of
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2008年第1期9-13,共5页
Chinese Journal of Infectious Diseases
基金
湖南省自然科学基金资助项目（03GGY3060）
关键词
雌二醇
纳米粒
肝硬化
Estradiol
Nanoparticles
Liver cirrhosis
