Brisset M, Pujol J P, Penfornis H, Farjanel J, Rattner A, Bocquet J, Béliard R, Loyau G
Int J Tissue React. 1986;8(4):271-8.
In order to get further insight into the mechanism of D-penicillamine action on synovial tissue collagen synthesis, fibroblasts derived from drug-treated arthritic rabbits were cultured and labelled with radioactive proline. No evident correlation was found between the amount of newly synthesized collagen and the previous treatment of animals. In contrast, the prolyl-hydroxylase activity was reduced in cells from rabbits receiving D-penicillamine. This finding suggests that culture conditions may influence the collagen-synthesizing potentiality of the synovial fibroblasts without changing the level of enzyme activity. Therefore, the prolyl-hydroxylase activity could be considered here as a more reliable reflection of the in vivo situation. The ratio of type III to type I procollagens, as estimated by DEAE-cellulose chromatography, showed a rise in cultures from D-penicillamine-treated rabbits as compared to controls. This result indicates that long-term administration of the drug may alter the collagen composition of synovial tissue matrix in rheumatoid arthritis. The question remains, however, whether this alteration contributes to the beneficial effect of the drug.
为了进一步深入了解D-青霉胺对滑膜组织胶原合成的作用机制，培养了取自经药物治疗的关节炎兔的成纤维细胞，并用放射性脯氨酸进行标记。新合成的胶原量与动物先前的治疗之间未发现明显的相关性。相反，接受D-青霉胺的兔的细胞中脯氨酰羟化酶活性降低。这一发现表明，培养条件可能影响滑膜成纤维细胞的胶原合成潜力，而不改变酶活性水平。因此，在此处脯氨酰羟化酶活性可被视为体内情况的更可靠反映。通过DEAE-纤维素色谱法估计，与对照组相比，来自D-青霉胺治疗兔的培养物中III型前胶原与I型前胶原的比例有所上升。这一结果表明，长期给药该药物可能会改变类风湿性关节炎滑膜组织基质的胶原组成。然而，问题仍然存在，即这种改变是否有助于药物的有益作用。
