首页|期刊导航|中华医学杂志（英文版）|Effects of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 on liver fibrosis in rats
中华医学杂志（英文版）2005，Vol.118Issue(3)：192-197,6.
Effects of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 on liver fibrosis in rats
Effects of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 on liver fibrosis in rats
摘要
Abstract
Background No efficient therapy for liver fibrosis has been available. This study was aimed to provide evidence that the introduction of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 (TIMP-1) into a rat model of immunologically induced liver fibrosis can result in the increased activity of interstitial collagenase, thus enhancing the degradation of collagen.Methods Real-time nested polymerase chain reaction (RT-Nested-PCR) and gene recombination techniques were used to construct a rat antisense TIMP-1 recombinant plasmid that can be expressed in eukaryotic cells. Both the recombinant plasmid and an empty vector (pcDNA3) were encapsulated with glycosyl-poly-L-lysine and injected into rats suffering from pig serum-induced liver fibrosis. The expression of exogenous transfected plasmid was assessed by Northern blot, RT-PCR, and Western blot. Hepatic interstitial collagenase activity was detected using fluorescinisothiocyanate (FITC)-labeled type Ⅰ collagen. In addition to hepatic hydroxyproline content, hepatic collagen types Ⅰ and Ⅲ were detected by immunohistochemical staining, and the stages of liver fibrosis by Van Gieson staining.Results Exogenous antisense TIMP-1 was successfully expressed in vivo and could block the gene and protein expression of TIMP-1. Active and latent hepatic interstitial collagenase activities were elevated (P<0.01), hepatic hydroxyproline content and the accumulation of collagen types Ⅰ and Ⅲ were lowered, and liver fibrosis was alleviated in the antisense TIMP-1 group (P<0.01) as compared with the model group. Conclusion The results demonstrate that antisense TIMP-1 recombinant plasmids have some inhibitory effect on liver fibrosis.关键词
liver fibrosis/antisense/tissue-inhibitor of metalloproteinase-1Key words
liver fibrosis/antisense/tissue-inhibitor of metalloproteinase-1引用本文复制引用
JIANG Wei,WANG Ji-yao,YANG Chang-qing,LIU Wen-bin,WANG Yi-qing,HE Bo-ming..Effects of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 on liver fibrosis in rats[J].中华医学杂志（英文版）,2005,118(3):192-197,6.基金项目
This study was supported by the National Natural Science Foundation of China (No. 39970339). （No. 39970339）
