【摘要】 目的研究抗凋亡蛋白BRE、TNFR1蛋白和自体吞噬蛋白Beclin1在小鼠肝纤维化的表达,并观察Reversine对其表达的影响。方法 24只昆明小鼠随机分为6组:第1组不作任何处理;第2组皮下注射0.1 mLCCl4/oil2,4 h后处死取肝组织;第3组皮下注射0.1 mL CCl4/oil4,8 h后处死;第4组皮下注射0.1 mL CCl4/oil,每周2次,连续注射6周,停止用药后15 d处死;第56、组方法同第4组,停止注射CCl4后分别用Reversine 501、00mg/(kg.d)皮下注射15 d,15 d后进行免疫组织化学检测,对BRE、TNFR1和Beclin1 3种蛋白的表达进行分析。结果免疫组化结果发现BRE、TNFR1和Beclin1 3种蛋白在CCl4诱肝纤维化过程中的表达明显上升,而经过纤维化抑制剂Reversine的处理后3种蛋白的表达下降至正常小鼠肝的水平。结论 BRE、TNFR1和Beclin1 3种应激反应分子可能在肝纤维化与肝炎发病中起重要作用,它们有可能成为肝病诊断标志物和治疗肝脏疾病的重要靶点。更多还原

【Abstract】 Objective To elucidate the molecular pathways in liver fibrosis with analysis of the expression of anti-apoptotic protein BRE and its binding partner TNFR1,and autophagy protein Beclin1 in mouse fibrotic-livers. Methods Liver fibrosis was induced in mice with carbon tetrachloride in 24 mice,which were randomly divided into 6 groups.Animals were administered with carbon tetrachloride s.c.twice per week for 6-weeks,after which the experimental groups were injected i.p.with a fibrotic inhibitor,Reversine.On 15th day post-treatment,all subjects were sacrificed for quantification of the the expression of BRE,TNFR1 and Beclin1 in livers by immunohistochemistry. Results Up-regulation of all 3 proteins were found in carbon tetrachloride-induced fibrotic livers,while their expressions were suppressed to normal levels in subjects with subsequent treatment of reversine. Conclusion Our data indicate that the stress-responsive molecules play important roles in the pathogenesis of liver fibrosis and hepatitis,and they could be used as diagnostic markers and therapeutic targets for liver diseases.更多还原