单糖或多糖修饰的超氧化物歧化酶衍生物对缺血/再灌注诱导的肝损伤的治疗作用

Therapeutic effects of superoxide dismutase derivatives modified with mono- or polysaccharides on hepatic injury induced by ischemia/reperfusion.

作者信息

Fujita T, Furitsu H, Nishikawa M, Takakura Y, Sezaki H, Hashida M

机构信息

Department of Basic Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

出版信息

Biochem Biophys Res Commun. 1992 Nov 30;189(1):191-6. doi: 10.1016/0006-291x(92)91543-y.

DOI:10.1016/0006-291x(92)91543-y

PMID:1449473

Abstract

Therapeutic effects of four types of recombinant superoxide dismutase (SOD) derivatives, conjugates with polysaccharides, carboxymethyl (SOD-CMD) and diethylaminoethyl (SOD-DEAED) dextrans and galactosylated (Gal-SOD) and mannosylated (Man-SOD) derivatives, on hepatic ischemia/reperfusion injury were studied in rats. Hepatic injury induced by transient occlusion and subsequent reflow of hepatic blood was evaluated by the analysis of biliary excretion of bromosulfophthalein (BSP) injected intravenously. At a dose of 10000 units/kg, native SOD and SOD-DEAE did not show any significant effect and SOD-CMD showed slight effect. On the other hand, Gal-SOD and Man-SOD, targeted to the liver parenchymal and nonparenchymal cells, respectively, by a receptor-mediated endocytosis, exhibited superior inhibitory effects. These results demonstrated that these glycosylated SOD derivatives were useful for the prevention of hepatic ischemia/reperfusion injury.

摘要

研究了四种重组超氧化物歧化酶（SOD）衍生物，即与多糖结合物、羧甲基（SOD-CMD）和二乙氨基乙基（SOD-DEAED）葡聚糖以及半乳糖基化（Gal-SOD）和甘露糖基化（Man-SOD）衍生物对大鼠肝缺血/再灌注损伤的治疗作用。通过分析静脉注射的溴磺酞钠（BSP）的胆汁排泄来评估短暂阻断肝血流并随后再灌注所诱导的肝损伤。在剂量为10000单位/千克时，天然SOD和SOD-DEAE未显示出任何显著效果，SOD-CMD显示出轻微效果。另一方面，分别通过受体介导的内吞作用靶向肝实质细胞和非实质细胞的Gal-SOD和Man-SOD表现出优异的抑制作用。这些结果表明，这些糖基化SOD衍生物可用于预防肝缺血/再灌注损伤。