Department of Basic Medicine, The Center of Translational Medicine, Xiamen Medical College, Xiamen 361023, China.
Department of Food Science, College of Life Sciences, National Taiwan Ocean University, Keelung 20224, Taiwan.
J Inorg Biochem. 2020 Sep;210:111172. doi: 10.1016/j.jinorgbio.2020.111172. Epub 2020 Jul 4.
Anemia is highly prevalent in people with chronic kidney disease (CKD), and CKD patients always have lower plasma but higher erythrocyte Zn levels than healthy people. To date, no satisfactory mechanism has explained these Zn metabolism abnormalities. We collected blood samples from patients on hemodialysis, 5/6 nephrectomized rats and phenylhydrazine (PHZ)-induced anemic mice and rats and compared them with their normal counterparts. We found that all the anemic animals had significantly decreased plasma Zn levels but elevated erythrocyte Zn levels. We also found that in anemic mice, new red blood cells (reticulocytes) had a ~7-fold higher Zn concentration than mature erythrocytes. When excess Zn was supplied to the rats, there was a ~1.2-fold increase in the Zn level in the rat bones. When Zn was depleted in the rats, the bones lost the greatest amount of Zn in the body (a 45% decrease). We prepared Zn-depleted rats and rendered these rats anemic by treating them with PHZ, and we compared them with normal rats. We found that in PHZ-induced anemia, rats released ~16% of Zn from their bones. Rat bones not only act as a 'reservoir' to adjust the excess or deficient Zn levels but also release Zn in anemia, and the released Zn stimulates erythropoiesis in the bone marrow. In anemia, Zn is redistributed from the plasma (causing the plasma Zn level to decreases) and bones to the bone marrow to produce reticulocytes (causing erythrocyte Zn level elevation).
贫血在慢性肾脏病（CKD）患者中非常普遍，CKD 患者的血浆锌水平总是低于健康人，而红细胞锌水平高于健康人。迄今为止，还没有令人满意的机制来解释这些锌代谢异常。我们收集了血液样本，分别来自血液透析患者、5/6 肾切除大鼠、苯肼（PHZ）诱导的贫血小鼠和大鼠，与正常对照组进行了比较。结果发现，所有贫血动物的血浆锌水平显著降低，而红细胞锌水平升高。我们还发现，在贫血小鼠中，新生的红细胞（网织红细胞）的锌浓度比成熟红细胞高约 7 倍。当给大鼠补充过量的锌时，大鼠骨骼中的锌含量增加了约 1.2 倍。当大鼠体内的锌被耗尽时，骨骼失去了体内最多的锌（减少了 45%）。我们制备了缺锌的大鼠，并用 PHZ 处理这些大鼠使其贫血，并与正常大鼠进行了比较。结果发现，在 PHZ 诱导的贫血中，大鼠从骨骼中释放了约 16%的锌。大鼠骨骼不仅作为一个“储备库”来调节过多或缺乏的锌水平，而且在贫血时释放锌，释放的锌刺激骨髓中的红细胞生成。在贫血中，锌从血浆（导致血浆锌水平降低）和骨骼重新分配到骨髓中，产生网织红细胞（导致红细胞锌水平升高）。
