Title: Effects of γ-interferon on gene expression of collagen I,III and tissue inhibitor of metalloproteinase 1 in dimethylnitrosamine induced liver fibrosis in rats
Abstract: Objective To observe the effects of γ-interferon (γ-IFN) on gene expression of collagen Ⅰ(Col Ⅰ),Ⅲ (Col Ⅲ) and tissue inhibitor of metalloproteinase 1(TIMP 1) in dimethylnitrosamine(DMN) induced liver fibrosis in rats.Methods Forty-five Wistar rats were randomized to divided into control group(15 rats), model group(15 rats) or γ-IFN prophylactic group(15 rats).0.5% DMN was injected intraperitoneally of 1 ml/kg body weight in model group and γ-IFN group with three consecutive shots in first week and two consecutive shots for the next five weeks, rats in the normal control group were treated with normal saline. In γ-IFN group, 10 5 U/kg body weight γ-IFN was injected daily subcutaneously for 8 weeks simultaneously. All rats were sacrificed at week 8 and liver tissues were taken for pathological examination, hepatic hydroxyproline determination. Gene expressions of Col Ⅰ,Col Ⅲ and TIMP1 were tested by reverse-transcription polymerase chain reaction(RT-PCR) and analyzed semi-quantificationally.Results Liver pathological examination showed grade 2 to 3 liver fibrosis in most model rats at week 6 after DMN injection and rars had some ascites. After stopping injection of DMN, liver fibrosis progressed to grade 3 and 4 at week 8, and ascites developed in most rats. In γ-IFN group the pathological changes were less pronounced and the severity of liver fibrosis was milder than grade 3. RT-PCR results that mRNA expression levels of Col Ⅰ, Col Ⅲ and TIMP1 in normal control group were 0.66±0.05, 0.59±0.05 and 0.56±0.04, respectivelty. In model group mRNA expression of Col Ⅰ, Col Ⅲ and TIMP1 elevated significantly (0.92±0.06, 0.75±0.07 and 0.91 ±0.07, respectively), the Col Ⅰ,Col Ⅲ and TIMP1 gene expression levels were reduced significantly to 0.73±0.06, 0.66±0.07 and 0.65±0.05 by the treatment of γ-IFN.Conclusion Col Ⅰ, Col Ⅲ and TIMP1 mRNA levels could be down regulated by γ-IFN in DMN induced liver fibrosis in rats, which maybe part of the antifibrotic mechanism of γ-IFN.
Publication Year: 2005
Publication Date: 2005-01-01
Language: en
Type: article
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Cited By Count: 1
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