γ-干扰素抑制肝纤维化大鼠Ⅰ、Ⅲ型胶原和基质金属蛋白酶组织抑制因子基因表达  

Effects of γ-interferon on gene expression of collagen Ⅰ,Ⅲ and tissue inhibitor of metalloproteinase 1 in dimethylnitrosamine induced liver fibrosis in rats

作　　者：马红[1] 朱跃科[1] 马雪梅[1] 贾继东[1] 王宝恩[1] 

机构地区：[1]首都医科大学附属北京友谊医院肝病中心,100050

出　　处：《肝脏》2005年第2期92-94,共3页Chinese Hepatology

基　　金：:北京市科技新星计划资助项目(954810500)

摘　　要：目的观察γ干扰素(γIFN)对二甲基亚硝胺(DMN)诱导肝纤维化大鼠肝脏Ⅰ型胶原(ColⅠ)、Ⅲ型胶原(ColⅢ)和基质金属蛋白酶组织抑制因子1(TIMP1)基因表达的作用。方法45只Wistar大鼠随机分为正常对照组(15只)、模型组(15只)和γIFN预防组(15只)。模型组用0.5%DMN10mgkg体重腹腔内注射,共6周,第1周连续3次,其后每周2次;γIFN预防组大鼠则在用DMN腹腔注射同时,每天皮下注射γIFN105Ukg体重,停止DMN注射后再用药2周,共8周。正常对照组以生理盐水腹腔内注射。于第8周处死大鼠,进行病理组织学检查、羟脯氨酸含量测定;以RTPCR法检测肝组织中ColⅠ、ColⅢ和TIMP1mRNA水平,BioRad凝胶成像系统对电泳结果进行半定量分析。结果肝组织病理检查显示,模型组大鼠在第6周停用DMN时,多数大鼠肝纤维化达2～3级,有的大鼠甚至出现腹水,停用DMN后,肝纤维化程度仍持续加重,至8周末所有大鼠肝纤维化达3～4级,且大多数伴有腹水。γIFN预防组病变较轻,最严重肝纤维化只有3级。RTPCR结果显示,正常对照组ColⅠ、ColⅢ、TIMP1mRNA表达水平分别为0.66±0.05、0.59±0.05、0.56±0.04,而模型组则分别为0.92±0.06、0.75±0.07、0.91±0.07,与对照组相比均明显升高,差异有统计学意义,γIFN预防组分别为0.73±0.06、0.66±0.07、0.66±0.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.

关 键 词：Γ-干扰素 肝纤维化 大鼠 Ⅰ型胶原 Ⅲ型胶原 基质金属蛋白酶组织抑制因子 基因表达 

分 类 号：R575.2[医药卫生—消化系统] R977[医药卫生—内科学]