THOMAS L, McCLUSKEY R T, POTTER J L, WEISSMANN G
J Exp Med. 1960 May 1;111(5):705-18. doi: 10.1084/jem.111.5.705.
The administration of large amounts of vitamin A to rabbits has been shown to result in depletion of cartilage matrix. The normal basophilic, metachromatic, and Alcian blue staining properties of the matrix are lost, especially in articular and epiphyseal cartilage. The cartilage cells remain intact, but are reduced in size. These changes sometimes appeared as early as 48 hours after the initiation of daily injection of 1 million units of vitamin A, and were usually well established by 5 days. Some rabbits failed to show changes in cartilage, even after 5 daily injections. Increased amounts of material presumed to be chondroitin sulfate were present in the sera of vitamin A-treated rabbits, usually by 72 hours after the first injection. This was demonstrated by a turbidimetric procedure using hexamminecobaltic chloride. In rabbits given sulfur-35 (Na(2)S(35)O(4)) 5 days before the initiation of vitamin A treatment, it was shown that sulfur-35 was lost from articular and epiphyseal cartilage. This was associated with an increase in the non-dialyzable sulfur-35 in both serum and in the cobalt-precipitable material. These rabbits also excreted more sulfur-35 than rabbits not given vitamin A. There was a reduction in sulfur-35 activity in chondromucoprotein extracted from the ear cartilage of vitamin A-treated rabbits. The changes are interpreted as indicating that the administration of large amounts of vitamin A to rabbits results in removal of chondroitin sulfate from cartilage matrix. The administration of small amounts of crude papain causes histologic changes in cartilage that are remarkably similar to those seen in vitamin A-treated rabbits. The possibility is suggested that the changes in cartilage produced by administration of vitamin A to rabbits may be the result of activation of a proteolytic enzyme or enzymes, with properties similar to those of papain.
已证明给兔子大量服用维生素A会导致软骨基质耗竭。基质正常的嗜碱性、异染性和阿尔辛蓝染色特性丧失，尤其是在关节软骨和骨骺软骨中。软骨细胞保持完整，但体积减小。这些变化有时在开始每日注射100万单位维生素A后48小时就出现了，通常在5天时就已很明显。一些兔子即使在每日注射5次后软骨也未出现变化。在维生素A处理的兔子血清中，通常在首次注射后72小时，推测为硫酸软骨素的物质含量增加。这通过使用氯化六氨合钴的比浊法得以证明。在维生素A处理开始前5天给兔子注射硫-35（Na₂S³⁵O₄），结果显示硫-35从关节软骨和骨骺软骨中流失。这与血清和钴沉淀物质中不可透析的硫-35增加有关。这些兔子排出的硫-35也比未服用维生素A的兔子多。从维生素A处理的兔子耳软骨中提取的软骨粘蛋白中的硫-35活性降低。这些变化被解释为表明给兔子大量服用维生素A会导致硫酸软骨素从软骨基质中去除。给兔子注射少量粗制木瓜蛋白酶会引起软骨的组织学变化，与维生素A处理的兔子中所见的变化非常相似。有人提出，给兔子服用维生素A所产生的软骨变化可能是一种或多种蛋白水解酶被激活的结果，这些酶的性质与木瓜蛋白酶相似。
