Radhakrishnamurthy B, Ruiz H, Dalferes E R, Klevay L M, Berenson G S
Department of Medicine, Louisiana State University Medical Center, New Orleans 70112.
Proc Soc Exp Biol Med. 1989 Jan;190(1):98-104. doi: 10.3181/00379727-190-42835.
Copper deficiency adversely affects the extracellular matrix of the arterial wall, leading to cardiovascular lesions. To study the lesions resulting from copper deficiency, the composition of proteoglycans from aortas of copper-deficient rats was compared with proteoglycans of aortas from copper-supplemented rats. Copper deficiency in rats was verified by copper levels in adrenal glands (mean +/- SE, 0.37 +/- 0.07 vs 1.03 +/- 0.17 micrograms/g wet wt in supplemented rats). The proteoglycans were isolated from the aorta by extraction with 4 M guanidine-HCl and by digestion of the tissue with elastase. The proteoglycans were purified by CsCl isopycnic centrifugation and fractionated by gel filtration. The fractions were characterized for molecular size and glycosaminoglycan composition. Total uronate in the aortas from copper-deficient rats was 25% greater than in aortas from copper-supplemented rats, and the proteoglycans from copper-deficient rat aortas were of greater molecular size. Among the glycosaminoglycans the concentration (microgram/mg tissue) of isomeric chondroitin sulfates, particularly dermatan sulfate, was greater in copper-deficient animals than in copper-supplemented animals. These observations are similar to earlier findings in experimental atherosclerosis and to a response of cardiovascular connective tissue to injury.
铜缺乏会对动脉壁的细胞外基质产生不利影响，从而导致心血管病变。为了研究铜缺乏导致的病变，将缺铜大鼠主动脉蛋白聚糖的组成与补铜大鼠主动脉蛋白聚糖的组成进行了比较。通过肾上腺中的铜含量验证大鼠的铜缺乏情况（平均值±标准误，缺铜大鼠为0.37±0.07微克/克湿重，补铜大鼠为1.03±0.17微克/克湿重）。通过用4M盐酸胍提取并使用弹性蛋白酶消化组织，从主动脉中分离出蛋白聚糖。通过氯化铯等密度离心法纯化蛋白聚糖，并通过凝胶过滤法进行分级分离。对各组分的分子大小和糖胺聚糖组成进行了表征。缺铜大鼠主动脉中的总糖醛酸比补铜大鼠主动脉中的总糖醛酸高25%，并且缺铜大鼠主动脉中的蛋白聚糖分子大小更大。在糖胺聚糖中，异构硫酸软骨素，特别是硫酸皮肤素的浓度（微克/毫克组织）在缺铜动物中比在补铜动物中更高。这些观察结果与早期实验性动脉粥样硬化的发现以及心血管结缔组织对损伤的反应相似。
