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聚乙二醇干扰素 α 2b 对胆管结扎诱导的大鼠肝纤维化的影响。

The effects of pegylated interferon alpha 2b on bile-duct ligation induced liver fibrosis in rats.

机构信息

Istanbul University Cerrahpasa Medical Faculty Department of Gastroenterology, Istanbul, Turkey.

出版信息

Ann Hepatol. 2009 Jul-Sep;8(3):234-40.

PMID:19841503
Abstract

OBJECTIVE

To test the effects of peginterferon in an unrecoverable model of bile-duct ligation (BDL) induced liver fibrosis.

MATERIAL AND METHODS

Thirty-seven Wistar rats were divided into five groups: group 1, BDL + peginterferon (n = 8); group 2, BDL (n = 8); group 3, sham + peginterferon (n = 7); group 4, sham (n = 7); and group 5, control group (n = 7). Peginterferon-alpha 2b (50 microgr/kg) or saline (1 mL/kg) was administered intraperitonealy every week for four weeks. Serum biochemical markers, liver tissue oxidative stress, collagen and transforming growth factor-beta (TGF-beta) levels were examined after four weeks. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining.

RESULTS

The levels of tissue collagen, TGF-beta, biochemical markers (AST, ALT, bilirubins, alkaline phosphates, gamma-glutamyl transpeptidase) and oxidative stress markers (Malondialdehyde, luminal, lucigenin) of the BDL group were higher than the sham operated and control groups (all-p < 0.001). Peginterferon improved malondialdehyde, luminal and glutathione levels in the BDL + peginterferon group (p < 0.05). Histopathological examination of the BDL groups showed stage-3 fibrosis, while all the control groups were normal. Peginterferon showed no improvement in fibrosis either histologically, or biochemically.

CONCLUSIONS

Peginterferon improved levels of malondialdehyde, glutathione and luminal in the rat model of BDL induced liver fibrosis. Peginterferon however,showed no anti-fibrotic effects in this model and therefore may not be a useful treatment for liver fibrosis.

摘要

目的

在不可逆转的胆管结扎(BDL)诱导的肝纤维化模型中测试聚乙二醇干扰素的作用。

材料和方法

37 只 Wistar 大鼠分为五组:第 1 组,BDL+聚乙二醇干扰素(n=8);第 2 组,BDL(n=8);第 3 组,假手术+聚乙二醇干扰素(n=7);第 4 组,假手术(n=7);第 5 组,对照组(n=7)。每周腹腔内注射聚乙二醇干扰素-α2b(50μg/kg)或生理盐水(1mL/kg),共四周。四周后检测血清生化标志物、肝组织氧化应激、胶原和转化生长因子-β(TGF-β)水平。肝组织切片行苏木精和伊红染色、马松三色染色和 Gomory 网染。

结果

BDL 组组织胶原、TGF-β、生化标志物(AST、ALT、胆红素、碱性磷酸酶、γ-谷氨酰转肽酶)和氧化应激标志物(丙二醛、腔隙、鲁米诺)水平均高于假手术组和对照组(均 p<0.001)。聚乙二醇干扰素改善了 BDL+聚乙二醇干扰素组的丙二醛、腔隙和谷胱甘肽水平(p<0.05)。BDL 组的组织病理学检查显示 3 期纤维化,而所有对照组均正常。聚乙二醇干扰素在组织学和生化水平上均未显示出改善纤维化的作用。

结论

聚乙二醇干扰素改善了 BDL 诱导的肝纤维化大鼠模型中丙二醛、谷胱甘肽和腔隙的水平。然而,聚乙二醇干扰素在该模型中没有显示出抗纤维化作用,因此可能不是治疗肝纤维化的有效方法。

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