Higuchi Yuriko, Kawakami Shigeru, Oka Machiko, Yabe Yoshiyuki, Yamashita Fumiyoshi, Hashida Mitsuru
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
FEBS Lett. 2006 Jun 26;580(15):3706-14. doi: 10.1016/j.febslet.2006.05.059.
The purpose of this study was to inhibit endotoxin induced cytokines production and liver injury by liver non-parenchymal cell (NPC) selective delivery of nuclear factor kappaB (NFkappaB) decoy using mannosylated cationic liposomes (Man-liposomes). In this study, we examined the distribution, inhibitory effect on cytokines production and ALT/AST of intravenously injected Man-liposome/NFkappaB decoy complex. Man-liposome/[(32)P] NFkappaB decoy complexes mostly accumulated in the liver, preferentially in NPC. In a murine lipopolysaccharide-induced liver failure model, the production of tumor necrosis factor-alpha (TNFalpha), IFNgamma, IL1-beta, ALT and AST were effectively reduced by Man-liposome complexes. However, cationic or galactosylated cationic liposome complexes could not inhibit TNFalpha production.
本研究的目的是通过甘露糖基化阳离子脂质体（甘露糖脂质体）将核因子κB（NFκB）诱饵选择性递送至肝非实质细胞（NPC），以抑制内毒素诱导的细胞因子产生和肝损伤。在本研究中，我们检测了静脉注射甘露糖脂质体/NFκB诱饵复合物的分布、对细胞因子产生的抑制作用以及ALT/AST水平。甘露糖脂质体/[(32)P]NFκB诱饵复合物大多积聚在肝脏，优先积聚在NPC中。在小鼠脂多糖诱导的肝衰竭模型中，甘露糖脂质体复合物可有效降低肿瘤坏死因子-α（TNFα）、IFNγ、IL1-β、ALT和AST的产生。然而，阳离子或半乳糖基化阳离子脂质体复合物不能抑制TNFα的产生。
