kielin／chordin样蛋白在肝纤维化模型中的动态表达及骨形成蛋白-7干预后的表达变化  

Dynamic expressions of kielin/chordin-like protein in mouse model of liver fibrosis and changes after bone morphogenetic protein-7 intervention

作　　者：宋梅[1] 陈永平[1] 陈少隆[1] 陈达之 阳韬[1] 林镯[1] 

机构地区：[1]温州医学院附属第一医院感染内科温州医学院肝病研究所,325000 [2]温州医学院仁济学院一系

出　　处：《中华传染病杂志》2012年第10期587-592,共6页Chinese Journal of Infectious Diseases

摘　　要：目的观察kielin／chordin样蛋白（kcp）在肝纤维化小鼠模型中的动态表达及骨形成蛋白-7（BMP-7）干预对其表达的影响，探讨治疗肝纤维化的新靶点。方法健康雄性ICR小鼠50只，分为正常对照组（10只）、模型组（30只）和BMP-7干预组（10只），模型组再按造模不同时间点分4、8、12周3个亚组，每组10只。模型组小鼠皮下注射四氯化碳制备肝纤维化小鼠模型，BMP-7干预组在造模后第8周开始腹腔注射人重组BMP-7，持续4周。造模后各组小鼠下腔静脉采血测定血清ALT、AST和Alb；肝组织经HE和Masson染色后光学显微镜下观察各组病理变化；采用RT-PCR、免疫组织化学和Western印迹法分别检测各组kcpmRNA及蛋白表达情况。各组间均数比较采用单因素方差分析。结果模型组血清AI。T、AST升高，Alb降低，12周时达峰值，BMP-7干预组有所缓解，各组间比较，差异有统计学意义（F值=23．501、34．600、16．244，均P〈0．05）。正常对照组kcpmRNA和蛋白表达很低，模型组则逐渐升高，BMP-7干预组有所缓解，差异有统计学意义（F值=30．362、10．727，P〈0．01或0．05）。kcpmRNA表达水平与转化生长因子81（TGF-131）、BMP-7mRNA表达水平均呈正相关（r=0．760、0．769，均P〈0．05）。结论BMP-7能改善小鼠肝纤维化；kcp可能参与肝纤维化发生发展过程，有望成为肝纤维化治疗的新靶点。Objective To observe the dynamic expressions of kielin/chordin-like protein （kcp） in mouse model of hepatic fibrosis and the effects of bone morphogenetic protein-7 （BMP-7） intervention on the expressions, and to explore a new target for treatment of fibrosis. Methods A total of 50 healthy male ICR mice were divided into three groups： control group（n= 10） ; model group （n=30） and BMP-7 treatment group （n= 10）. The model group was further divided into three subgroups according to different time points： subgroups of 4, 8 and 12 weeks with 10 mice in each subgroup. The mouse model of hepatic fibrosis was established by hypodermic injection of carbon tetrachloride（CC14 ）. The mice in BMP-7 treatment group began to receive human recombinant BMP-7 via intraperitoneai injection after 8 weeks of the first administration of CC14 and lasted for 4 weeks. The serum levels of alanine aminotransferase （ALT）, aspartate transaminase （AST） and albumin （Alb） were detected. The pathological changes of liver were observed under optical microscope after HE and Masson staining. The dynamic expressions of kcp mRNA and protein of each group were detected by reverse transcription-polymerase chain reaction, immunohistochemistry and Western blot. The comparison of means among groups was done by univariate ANOVA. Results In model group, ALT and AST levels increased, while Alb level gradually decreased, and peaked at week 12. BMP-7 treatment could reduce the changes, and there were significant differences among groups （F= 23. 501, 34. 600 and 16. 244, respectively; all P〈0.05）. In normal control group, the expressions of kcp mRNA and protein were low, while those in model group were gradually increased. BMP-7 treatment could achieve remission and the changes were all significantly different among groups （F= 30. 362 and 10. 727, respectively; P〈0.01 or 0.05）. The expression of kcp mRNA was positively correlated with levels of transforming growth factor （TGF）-β1 mRNA and BMP-7 mRNA （r=

关 键 词：骨形态发生蛋白质类 转化生长因子Β1 RNA 信使 肝硬化 疾病模型 动物 

分 类 号：R575.2[医药卫生—消化系统]