以TIMP-2为靶基因的反义寡核苷酸对肝纤维化大鼠肝功能生化和肝纤维化指标的影响  

Effect of TIMP-2 targeting antisense oligonucleotide on liver function and fibrosis profiles in rat model of liver fibrosis

作　　者：张亚飞[1] 聂青和[1] 徐辉[2] 谢玉梅[1] 邵彬[1] 

机构地区：[1]第四军医大学唐都医院传染病科全军感染病诊疗中心,陕西西安710038 [2]第四军医大学唐都医院消化科

出　　处：《肝脏》2005年第4期291-293,共3页Chinese Hepatology

基　　金：中国博士后科学基金资助项目(中博基[1999]10号);陕西省科技攻关项目(2003K10G63)

摘　　要：目的探讨以基质金属蛋白酶组织抑制因子-2(TIMP-2)为靶基因的反义寡核苷酸对肝纤维化大鼠肝功能生化和肝纤维化指标的影响。方法免疫诱导型大鼠肝纤维化模型制备过程中,尾静脉注射针对TIMP-2的反义寡核苷酸。模型制备结束后,检测ALT、ALP、TBil、DBil等肝功能生化指标和血清HA、Ⅳ-C、PCⅢ水平等肝纤维化指标,并测定肝组织羟脯氨酸含量,分析治疗组与其他实验组间的差异。结果治疗组肝功能生化各指标均优于模型组和秋水仙碱组;治疗组肝纤维化生化指标与模型组和秋水仙碱组相比,其数值较低,但差异不显著;治疗组肝组织羟脯氨酸含量显著低于模型组和秋水仙碱组。结论抑制TIMP-2在肝组织中的表达可抑制细胞外基质(ECM)在肝组织内的沉积,降低肝纤维化大鼠肝脏功能的损害。Objective To investigate the effect of TIMP-2 targeting antisense oligonucleotide （asON） on liver function and fibrosis index in rat liver fibrosis model. Methods Using TIMP-2 targeting asON to inhibit the expression of TIMP-2 in fibrosis liver. Profiles of liver function and fibrosis were tested to analyze the effect of inhibited TIMP-2 expression on rat liver fibrosis. Results Liver function of asON treated group was better in comparison with model group and colchicine group. Serum fibrosis profiles of asON treated group were a little better, but the improvement was not statistically significant. The content of hydroxyproline in fibrotic liver tissue in asON treated group was significantly lower than that of model group and colchlcine group. Conclusion Inhibited expression of TIMP-2 could decrease the deposition of ECM in rat fibrotic liver tissue, and improve the liver function.

关 键 词：反义寡核苷酸 基质金属蛋白酶组织抑制因子-2 大鼠 肝纤维化 肝功能 肝纤维化指标 

分 类 号：R575.2[医药卫生—消化系统]