Riley D J, Kerr J S, Yu S Y
Toxicol Appl Pharmacol. 1984 Sep 30;75(3):554-60. doi: 10.1016/0041-008x(84)90192-3.
Proline analogs inhibit collagen biosynthesis and prevent accumulation of collagen in tissues. The antifibrotic effects of three proline analogs, cis-hydroxyproline, L-azetidine-2-carboxylic acid, and L-3,4-dehydroproline, were compared in a rat oxygen toxicity model. The specificity of these agents for collagen was examined by measuring their effects on noncollagen protein and elastin accumulation in the lung. Increased lung collagen was produced by exposing rats to 95% O2 for 60 hr followed by a 2-week recovery period. Animals were treated with the proline analogs for the 2-week period. Oxygen exposure in untreated animals increased lung collagen 26% above air-breathing controls, and this increase was prevented by all three analogs. Increased noncollagen protein was also prevented by these agents, suggesting they were not entirely specific for collagen. Elastin accumulation, however, was not inhibited by cis-hydroxyproline. It was concluded that proline analogs were antifibrotic, but affected the metabolism of noncollagen protein.
脯氨酸类似物可抑制胶原蛋白的生物合成，并防止胶原蛋白在组织中积累。在大鼠氧中毒模型中比较了三种脯氨酸类似物，即顺式羟脯氨酸、L-氮杂环丁烷-2-羧酸和L-3,4-脱氢脯氨酸的抗纤维化作用。通过测量它们对肺中非胶原蛋白和弹性蛋白积累的影响来检验这些药物对胶原蛋白的特异性。将大鼠暴露于95%氧气中60小时，随后经过2周的恢复期，从而使肺胶原蛋白增加。在这2周期间用脯氨酸类似物对动物进行治疗。未治疗动物的氧气暴露使肺胶原蛋白比呼吸空气的对照组增加了26%，而所有三种类似物都可防止这种增加。这些药物也可防止非胶原蛋白增加，这表明它们并非完全对胶原蛋白具有特异性。然而，顺式羟脯氨酸并未抑制弹性蛋白的积累。得出的结论是，脯氨酸类似物具有抗纤维化作用，但会影响非胶原蛋白的代谢。
