Studies on the uptake mechanism of liposomes by perfused rat liver. II. An indispensable factor for liver uptake in serum.
Studies on the uptake mechanism of liposomes by perfused rat liver. II. An indispensable factor for liver uptake in serum.
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灌注大鼠肝脏摄取脂质体机制的研究
DOI：
10.1248/cpb.35.1189
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发表时间：
1987
影响因子：
1.7
通讯作者：
Y. Kato
中科院分区：
文献类型：
--
作者：
H. Kiwada;T. Miyajima;Y. Kato
在小容量循环灌注系统中，研究了肝脏摄取脂质体的参与因素。灌注液的体积为23 ml，其对应于大鼠的血容量。认为该系统适用于检查参与体内摄取的因素。在新鲜血清中发现了一种摄取不可缺少的因子，其摄取量与血清中因子的量成正比。用不同方法预处理的血清研究了该因子的性质。用预热血清进行的实验表明，该因子对热非常敏感，可能是一种蛋白质。当血清用纤维素膜透析时，活性透过膜，其分子量被推断为低于17000道尔顿。平衡透析时膜两侧酶活性之和与新鲜血清中酶活性之和基本相等。这有力地表明，该因子不与其他因子合作参与吸收。当血清与脂质体在38 °C预先孵育5min时，摄取活性消失。该因子与脂质体的相互作用似乎是非常快速和不可逆的。还检查了静脉注射后肝脏的摄取和灌注系统中灌注液的消除与体内行为的对应关系。观察到相应的摄取，但从灌流液和血液中的消除动力学是不同的。这表明，吸收是由这里描述的因素，但消除动力学部分受其他因素的影响。
Participating factors in the uptake of liposomes by the liver were examined in a small-volume circulating perfusion system. The volume of the perfusate was 23 ml, which corresponds to the blood volume of the rat. It is considered that this system is suitable for examining the factors participating in the uptake in vivo. An indispensable factor for the uptake was found in fresh serum, and the uptake proportionally depended on the amount of the factor in serum. The properties of the factor were investigated with serum pretreated in various ways. The experiment with preheated serum indicated that the factor is very heat-sensitive and may be a protein. When serum was dialyzed with a cellulose membrane, the activity penetrated through the membrane, and its molecular weight was concluded to be below 17000 daltons. The sum of the activities on both sides of the membrane in equilibrium dialysis was almost equal to that in fresh serum. This strongly suggests that the factor does not participate cooperatively with other factors in the uptake. The uptake activity disappeared when serum was incubated with liposomes at 38 °C for 5 min in advance. The interaction of the factor with liposomes appears to be very fast and irreversible.Correspondence of the uptake by the liver and elimination from the perfusate in the perfusion system to the in vivo behavior after i.v. injection was also examined. Correspondence of the uptake was observed, but the elimination kinetics from perfusate and blood were different. It is suggested that the uptake is dominated by the factor described here, but the elimination kinetics is partially affected by other factor (s).