Karzel K, Breuer N A
Institut für Pharmakologie und Toxikologie der Universität Bonn.
Arzneimittelforschung. 1988 Sep;38(9):1327-33.
The glycosaminoglycan (GAG) distribution pattern of murine fetal tibiae cultured for 6 days in vitro was determined and the effects of drugs on the growth of the tibia explants in vitro, on their total GAG content and on their GAG distribution pattern were studied. The explants contained chondroitin-4-sulfate and chondroitin-6-sulfate in a relation of about 4:1; hyaluronic acid was not detected. During the incubation period of 6 days in vitro a mean increase in size of 47% and of the total GAG content of about 80-90% was observed; the GAG distribution pattern was practically unchanged. Incubation of the explants in a medium without ascorbic acid by contrast to a medium containing ascorbic acid (5 and 50 micrograms/ml) lead to a reduction of growth and total GAG content. The nonsteroidal antiphlogistic drugs phenylbutazone (20 and 200 micrograms/ml), ibuprofen (25 and 200 micrograms/ml) and alclofenac (25 and 400 micrograms/ml) effected a concentration dependent decrease of the growth and of the GAG content of the explants mainly due to a reduction of chondroitin-4-sulfate. Prednisolone (10 micrograms/ml) caused a significant increase of the GAG content of the explants leaving their GAG distribution pattern nearly unchanged. Aurothioglucose (400 micrograms/ml) induced a reduction of the growth and of the GAG content of the explants without altering the GAG distribution. Under low concentrations of Na-pentosanpolysulfate (5 micrograms/ml) an increase in growth and in the GAG content by a nearly unaltered GAG distribution pattern was observed, high concentrations (200 micrograms/ml), however, caused a reduction of growth and of the GAG content.
测定了在体外培养6天的小鼠胎儿胫骨的糖胺聚糖(GAG)分布模式,并研究了药物对胫骨外植体体外生长、其总GAG含量及其GAG分布模式的影响。外植体中硫酸软骨素-4和硫酸软骨素-6的含量比例约为4:1;未检测到透明质酸。在体外6天的培养期内,观察到大小平均增加47%,总GAG含量增加约80 - 90%;GAG分布模式基本未变。与含有抗坏血酸(5和50微克/毫升)的培养基相比,将外植体培养在不含抗坏血酸的培养基中会导致生长和总GAG含量降低。非甾体抗炎药保泰松(20和200微克/毫升)、布洛芬(25和200微克/毫升)和氯芬酸(25和400微克/毫升)主要由于硫酸软骨素-4减少而使外植体的生长和GAG含量呈浓度依赖性降低。泼尼松龙(10微克/毫升)使外植体的GAG含量显著增加,而其GAG分布模式几乎不变。金硫葡萄糖(400微克/毫升)导致外植体的生长和GAG含量降低,而不改变GAG分布。在低浓度的戊聚糖多硫酸钠(5微克/毫升)作用下,观察到生长和GAG含量增加,GAG分布模式几乎未变,然而高浓度(200微克/毫升)则导致生长和GAG含量降低。