Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis

Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis
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DOI:
10.1053/gast.1997.v113.pm9352873
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发表时间:
1997-11-01
期刊:
影响因子:
29.4
通讯作者:
Prieto, J
Prieto, J
中科院分区:
医学1区
文献类型:
--
作者:
CastillaCortazar, I;Garcia, M;Prieto, J

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背景与目的:肝硬化患者胰岛素样生长因子(IGF-I)的生物利用度降低。本研究的目的是分析IGF-I对实验性肝硬化肝组织病理学和功能的影响。研究方法:大鼠吸入CCl 4 11或30周(分别为方案1和2),并在第13和14周(方案1)或第28-30周(方案2)用2 μ g/100 g体重(-1)天(-1)IGF-I(CI + IGF组)或盐水(CI组)处理。正常大鼠进行了平行研究。结果:与正常大鼠相比,CI组血清白蛋白和总蛋白水平降低,而CI + IGF组血清白蛋白和总蛋白水平无变化。CI + IGF组的凝血因子II、VII和X显著高于CI组。CI大鼠肝脏脂质过氧化产物显着增加,但CI + IGF大鼠则无此变化,CI + IGF大鼠的肝纤维化程度低于CI动物。与正常动物相比,CI组抗氧化酶活性和线粒体跨膜电位降低,而CI + IGF组则无此变化。结论:IGF-I改善了代偿期或晚期肝硬化大鼠的肝功能,减轻了氧化性肝损伤和纤维化。改善线粒体功能可能在这种激素的保肝作用中发挥作用。
Background & Aims: Bioavailability of insulin-like growth factor (IGF-I) is reduced in liver cirrhosis. The aim of this study was to analyze the effect of IGF-I on liver histopathology and function in experimental cirrhosis. Methods: Rats received CCl4 inhalations for 11 or 30 weeks (protocols 1 and 2, respectively) and were treated with 2 mu g.100 g body wt(-1).day(-1) IGF-I (group CI + IGF) or saline (group CI) on weeks 13 and 14 (protocol 1) or on weeks 28-30 (protocol 2). Normal rats were studied in parallel. Results: Serum albumin and total protein levels were reduced in CI but not in CI + IGF rats compared with normal rats. Clotting factors II, VII, and X were significantly greater in CI + IGF than in CI rats. Liver lipid peroxidation products were significantly increased in CI but not in CI + IGF rats, and liver fibrosis was less pronounced in CI + IGF than in CI animals. The activities of antioxidant enzymes and mitochondrial transmembrane potential were reduced compared with normal animals in CI but not in CI + IGF rats. Conclusions: IGF-I improves liver function and reduces oxidative liver damage and fibrosis in rats with compensated or advanced liver cirrhosis. Improved mitochondrial function could play a role in the hepatoprotective effect of this hormone.