Department of Food Science, College of Life Sciences, National Taiwan Ocean University, Keelung 20224, Taiwan.
Department of Basic Medicine, The Center of Translational Medicine, Xiamen Medical College, Xiamen 361023, China.
Int J Mol Sci. 2019 Oct 9;20(20):4985. doi: 10.3390/ijms20204985.
Anemia is a severe complication in patients with chronic kidney disease (CKD). Treatment with exogenous erythropoietin (EPO) can correct anemia in many with CKD. We produced 5/6-nephrectomized rats that became uremic and anemic at 25 days post surgery. Injection of the anemic 5/6-nephrectomized rats with 2.8 mg zinc/kg body weight raised their red blood cell (RBC) levels from approximately 85% of the control to 95% in one day and continued for 4 days. We compared the effect of ZnSO and recombinant human erythropoietin (rHuEPO) injections on relieving anemia in 5/6-nephrectomized rats. After three consecutive injections, both the ZnSO and rHuEPO groups had significantly higher RBC levels (98 ± 6% and 102 ± 6% of the control) than the saline group (90 ± 3% of the control). In vivo, zinc relieved anemia in 5/6-nephrectomized rats similar to rHuEPO. In vitro, we cultured rat bone marrow cells supplemented with ZnCl, rHuEPO, or saline. In a 4-day suspension culture, we found that zinc induced erythropoiesis similar to rHuEPO. When rat bone marrow cells were supplement-cultured with zinc, we found that zinc stimulated the production of EPO in the culture medium and that the level of EPO produced was dependent on the concentration of zinc supplemented. The production of EPO via zinc supplementation was involved in the process of erythropoiesis.
贫血是慢性肾脏病（CKD）患者的严重并发症。用外源性促红细胞生成素（EPO）治疗可以纠正许多 CKD 患者的贫血。我们制作了 5/6 肾切除术大鼠，这些大鼠在手术后 25 天变成尿毒症和贫血。给贫血的 5/6 肾切除术大鼠注射 2.8 毫克/公斤体重的锌，可使红细胞（RBC）水平在一天内从对照组的约 85%提高到 95%，并持续 4 天。我们比较了 ZnSO 和重组人促红细胞生成素（rHuEPO）注射对缓解 5/6 肾切除术大鼠贫血的影响。连续三次注射后，ZnSO 和 rHuEPO 组的 RBC 水平均明显高于对照组（分别为对照组的 98±6%和 102±6%），而生理盐水组仅为对照组的 90±3%。在体内，锌与 rHuEPO 一样可缓解 5/6 肾切除大鼠的贫血。在体外，我们培养补充 ZnCl、rHuEPO 或生理盐水的大鼠骨髓细胞。在为期 4 天的悬浮培养中，我们发现锌诱导红细胞生成的作用与 rHuEPO 相似。当大鼠骨髓细胞补充锌培养时，我们发现锌刺激培养基中 EPO 的产生，并且产生的 EPO 水平取决于补充的锌浓度。通过补充锌产生 EPO 参与了红细胞生成过程。
