基质金属蛋白酶-1、反义金属蛋白酶组织抑制因子-1表达质粒对大鼠肝纤维化的影响  

Effects of matrix metalloproteinase-1 and antisense tissue inhibitor of metalloproteinase-1 recombinant plasmid on rat liver fibrosis

作　　者：杨长青[1] 胡国龄[1] 谭德明[1] 张铮[1] 

机构地区：[1]湖南医科大学湘雅医院传染病研究所

出　　处：《中华传染病杂志》2000年第1期29-32,共4页Chinese Journal of Infectious Diseases

摘　　要：目的　观察基质金属蛋白酶1(MMP1)、反义金属蛋白酶组织抑制因子1(TIMP1) 表达质粒对大鼠肝纤维化的影响。方法　运用重组DNA 技术,构建大鼠MMP1 、反义TIMP1 真核细胞表达质粒,经脂质体包埋后,利用腹腔注射将其导入免疫性大鼠肝纤维化模型体内,观察其对大鼠肝纤维化的影响。结果　MMP1 、反义TIMP1 表达质粒均可促进肝脏中Ⅰ、Ⅲ型胶原的降解( P<0 .05 ～P< 0.01) ,且作用较秋水仙碱为强( P< 0.05) ;在病理形态学的观察方面,MMP1 、反义TIMP1 表达质粒对肝纤维化有一定的逆转作用( P< 0.05),但MMP1 表达质粒与秋水仙碱相比差异无显著性( P>0 .05) 。结论　MMP1、反义TIMP1 表达质粒对肝纤维化均有不同程度的逆转作用,以两种质粒的联合应用效果最为明显,单独使用反义TIMP1 表达质粒次之,单独使用MMP1 表达质粒作用有限。Objective To study the effects of matrix metalloproteinase 1 (MMP 1) and antisense tissue inhibitor of metalloproteinase 1 (TIMP 1) recombinant plasmid on rat liver fibrosis. Methods We constructed the rat's MMP 1 and antisense TIMP 1 recombinant plasmids by reverse transcription nested polymerase chain reaction (RT Nested PCR) and the technique of DNA recombination. After encapsulated by lipofectin, the MMP 1 and/or antisense TIMP 1 recombinant plasmids was transferred to the rats with liver fibrosis in vivo intraperitoneally, then the effects of the plasmids on the hepatic fibrosis were observed by RT PCR for MMP 1 and TIMP 1, immunohistochemical assay for type Ⅰ and type Ⅲ collagen, and Masson staining for the observation of pathology. Results The recombinant plasmids of MMP 1 and antisense TIMP 1 could enhance the degradation of type Ⅰ and type Ⅲ collagen in the rat's fibrotic liver compared with fibrotic modal group ( P <0.01 ) or compared with colchicine treated group ( P <0.05). Moreover the recombinant plasmids of MMP 1 and antisense TIMP 1 have some reverse effects on the hepatic fibrosis compared with fibrotic modal group ( P<0.01～P<0.05 ), but no obvious difference was found between the groups of plasmid of MMP 1 and colchicine ( P >0.05). Conclusion The recombinant plasmids of MMP 1 and antisense TIMP 1 have some reverse effects on hepatic fibrosis to a greater or less degree. Using the two plasmids together has the stronger effect than using the plasmid of antisense TIMP 1 alone and using the plasmid of MMP 1 only lead to a limited changes.

关 键 词：肝硬化 肝纤维化 质粒 MMP-1 TIMP-1 

分 类 号：R459.9[医药卫生—治疗学]