聚乙二醇超氧化物歧化酶衍生物：对大鼠角叉菜胶性胸膜炎的抗炎活性

PEG superoxide dismutase derivatives: anti-inflammatory activity in carrageenan pelurisy in rats.

作者信息

Conforti A, Franco L, Milanino R, Velo G P, Bocc+53u E, Largajolli E, Schiavon O, Veronese F M

机构信息

Istituto di Farmacologia, University of Verona, Italy.

出版信息

Pharmacol Res Commun. 1987 Apr;19(4):287-94. doi: 10.1016/0031-6989(87)90086-5.

DOI:10.1016/0031-6989(87)90086-5

PMID:3659113

Abstract

Two derivatives of superoxide dismutase (SOD) with monomethoxypolyethyleneglycol, having different molecular weights (46,000 and 121,000 D) and different plasma half-lives are tested in carrageenan pleurisy in rats after single i.v. injection. The compounds were prepared following an original method where the polymer is activated by trichlorophenylchloroformate to give a phenylcarbonate which is reactive towards the protein amino groups. The anti-inflammatory activity of derivatives results correlated to their kinetics, lasting longer for the derivative with the longest half-life (SOD-PEG 18). SOD activity, in plasma of rats treated with SOD-PEG 18, is still present 24 hour after carrageenan, in agreement with the prolonged anti-inflammatory activity. Moreover SOD-PEG 18 diffuses well in pleural exudate, as it is evidentiated from the increase with time of exudate/plasma concentration ratio.

摘要

用单甲氧基聚乙二醇制备的两种超氧化物歧化酶（SOD）衍生物，具有不同的分子量（46,000和121,000 D）和不同的血浆半衰期，在大鼠静脉单次注射后用于角叉菜胶性胸膜炎实验。这些化合物按照一种原始方法制备，其中聚合物用三氯苯基氯甲酸酯活化生成对蛋白质氨基有反应性的苯基碳酸酯。衍生物的抗炎活性结果与其动力学相关，半衰期最长的衍生物（SOD-PEG 18）的抗炎活性持续时间更长。在用SOD-PEG 18处理的大鼠血浆中，角叉菜胶注射24小时后仍存在SOD活性，这与延长的抗炎活性一致。此外，SOD-PEG 18在胸膜渗出液中扩散良好，从渗出液/血浆浓度比随时间的增加可以明显看出。