文章基本信息

标题：Influence of Murine Hepatitis Induced by D-(+)-Galactosamine Hydrochloride and Lipopolysaccharide on Gene Expression of Polyethylenimine/plasmid DNA Polyplex
本地全文：下载
作者：Kei Miyanaga ; Takashi Yoshioka ; Hiroo Nakagawa 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：8
页码：1585-1589
DOI：10.1248/bpb.31.1585
出版社：The Pharmaceutical Society of Japan
摘要：We investigated the influence of murine hepatitis induced by D -(+)-galactosamine and lipopolysaccharide ( D -GalN/LPS) on polyethylenimine (PEI)-mediated plasmid DNA (pDNA) delivery. pDNA encoding firefly luciferase was used as the model reporter gene. PEI was used as the non-viral vector because of its high gene expression and low toxicity. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice indicated the highest peaks at 12 h after D -GalN/LPS injection, then the activities of serum ALT and AST rapidly decreased. We determined luciferase activity in various organs of D -GalN/LPS-treated mice and control mice after an intravenous administration of PEI/pDNA complexes. High transgene expression was observed in the liver, spleen, and lung of both mice. Compared to the control mice, a significant increase of transgene expression was observed in the liver of D -GalN/LPS-treated mice after D -GalN/LPS injection. The transgene expression in the spleen and lung decreased at 6 and 12 h after D -GalN/LPS injection. In conclusion, we found that murine hepatitis induced by D -GalN/LPS injection can influence PEI-mediated pDNA delivery and its influence was different from that induced by CCl₄ injection which was reported previously. These results demonstrated the necessity of considering the timing and dose of gene therapy according to the disease and its stage.
关键词：gene delivery;polyethylenimine;murine hepatitis;non-viral vector;disease stage