Hepatic Disposition Characteristics of Electrically Charged Macromolecules in Rat in Vivo and in the Perfused Liver
Hepatic Disposition Characteristics of Electrically Charged Macromolecules in Rat in Vivo and in the Perfused Liver
复制标题
大鼠体内和灌注肝脏中带电大分子的肝脏分布特征
作者：
K. Nishida;K. Mihara;T. Takino;S. Nakane;Y. Takakura;M. Hashida;H. Sezaki
研究了电荷对大鼠肝脏大分子处置的影响。葡聚糖 (T-70) 和牛血清白蛋白 (BSA) 的带电衍生物、丝裂霉素 C-葡聚糖缀合物 (MMC-D) 和乳糖化 BSA (Lac-BSA) 被用作模型大分子。静脉注射后，阳离子大分子因其广泛的肝脏摄取而迅速从血浆中消除，而阴离子和中性大分子则缓慢消除。从实质和非实质肝细胞中回收阳离子大分子，细胞摄取（每单位细胞数）比率为1.4-3.2，而Lac-BSA为14。在使用单次恒定输注模式的肝脏灌注过程中，阳离子大分子被肝脏持续提取，稳态提取比率（Ess）范围在0.03至0.03之间。 0.54，而阴离子和中性大分子在稳态流出物中几乎完全恢复。阳离子化 BSA (Cat-BSA) 和阳离子 MMC-Dcat 的 Ess 具有浓度依赖性，并且在低温和秋水仙碱和细胞松弛素 B 存在下会降低。表明内化过程可能参与肝细胞摄取阳离子大分子。
The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C–dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4–3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (Ess) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The Ess for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested.
DOI：
10.1016/s0021-9258(18)34710-0
发表时间：
1982-04
期刊：
The Journal of biological chemistry
影响因子：
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作者：
A. Schwartz;S. E. Fridovich;H. Lodish
通讯作者：
A. Schwartz;S. E. Fridovich;H. Lodish