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白蛋白功能的分子层面:其在血浆置换中应用的指征

Molecular aspects of albumin functions: indications for its use in plasma substitution.

作者信息

Zilg H, Schneider H, Seiler F R

出版信息

Dev Biol Stand. 1980;48:31-42.

PMID:7274562
Abstract

The maintenance of the circulating fluid within the vascular system is a major role of plasma albumin. Besides its role as a protein reservoir the third function of albumin is its ability to bind and transport metabolic products, regulatory mediators, nutrients and proteins and to bind and neutralize endogenous or exogenous toxins. Bilirubin binding was chosen as a method to describe functional quality of albumin preparations. Binding at the high affinity site is well preserved in all commercial albumin-containing plasma substitutes investigated with KA values in the range of 3.2 to 4.8 . 10(7) 1/mol. Presence of absence of conventional stabilizers does not influence binding characteristics since heating of products according to various pharmacopoeia levels out any difference. The importance of ligand binding properties of a plasma substitute is stressed either in intoxications, e.g. hyperbilirubinemia of neonates or in surgical situations were multiple drug applications might disturb a balanced binding situation. Though relatively mild in nature and less frequently observed in comparison with artificial plasma substitutes incidence of adverse reactions in connection with albumin was used to search for causes. Biochemical parameters like residual proteolytic activity in general or specified (prekallikrein activator), content of aggregates, anti-complementary activity and influence on granulocyte activity did not give any clear answer in this task, neither did pharmacological testing designed to detect factors leading to histamine and kinin liberation or to detect pyrogens.

摘要

维持血管系统内循环液体是血浆白蛋白的主要功能。除了作为蛋白质储备的作用外,白蛋白的第三个功能是其结合和运输代谢产物、调节介质、营养物质和蛋白质以及结合和中和内源性或外源性毒素的能力。选择胆红素结合作为描述白蛋白制剂功能质量的方法。在所研究的所有含白蛋白的商业血浆代用品中,高亲和力位点的结合都得到了很好的保留,其解离常数(KA)值在3.2至4.8×10⁷ 1/mol范围内。常规稳定剂的有无并不影响结合特性,因为根据各种药典对产品进行加热可消除任何差异。血浆代用品的配体结合特性的重要性在中毒情况(如新生儿高胆红素血症)或手术情况下得到强调,在手术中多种药物的应用可能会扰乱平衡的结合情况。尽管与人工血浆代用品相比,白蛋白相关不良反应的性质相对较轻且较少见,但仍用其来寻找原因。诸如一般或特定的残余蛋白水解活性(前激肽释放酶激活剂)、聚集体含量、抗补体活性以及对粒细胞活性的影响等生化参数,在这项任务中均未给出明确答案,旨在检测导致组胺和激肽释放的因素或检测热原的药理学测试也未给出明确答案。

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