尿毒症毒素对大鼠培养骨髓细胞红细胞生成素受体的影响

目的 通过观察尿毒症毒素对骨髓红系祖细胞红细胞生成素受体(EPOR)的影响，探讨EPOR抑制在尿毒症肾性贫血发生发展中的作用。方法 对大鼠骨髓红系祖细胞进行培养，观察尿毒症的小分子毒素尿素、肌酐、尿酸、精脒，中分子物质(MMS)，大分子毒素甲状旁腺激素(PTH)在不同浓度时红系祖细胞克隆形成单位(CFU-E)的生长情况，并用RT-PCR法测定其EPOR mRNA表达，Western Blot分析EPOR蛋白质合量。结果 尿素、肌酐、尿酸和PTH对CFU-E的生长有抑制作用，精脒和MMS在较低浓度时即对CFU-E的生长具有显著的抑制作用;小分子毒素、MMS对EPORmRNA表达和EPOR蛋白质含量具有普遍的抑制作用。结论 尿毒症毒素可抑制离体大鼠红系祖细胞CFU-E的生长和其EPOR表达，其中精脒和MMS显著抑制CFU-E生长，是引起肾性贫血的重要原因之一。

Effects of some uremic toxins on erythropoietin receptor of CFU-E of rats in vitro

Objective To explore the important role of erythropoietin receptor (EPOR) in the mechanisms of renal anemia by observing the inhibitory effect of the uremic toxins on EPOR of clone forming unit erythroid(CFU E) of rat bone marrow in vitro.Methods Uremic toxins including creatinine, urea, Uric acid, spermidine, middle molecule substances (MMS) and parathyroid hormone (PTH) were co incubated in different concentration with mononuclear cells of rat bone marrow respectively for 7 days. Counted the number of CFU E with inverted microscope, examined the expression of EPORmRNA by RT PCR technique and assayed the content of EPOR protein by Western Blot analysis.Results Creatinine, urea, uric acid and PTH had inhibitory effect on CFU E growth of rat bone marrow in vitro. Spermidine and MMS inhibited the most significantly. All the uremic toxins except had inhibitory effect on the expression of EPORmRNA and the amount of EPOR protein.Conclusion Uremic toxins can inhibit the expression of EPOR on CFU E of rat's bone marrow. And the EPOR inhibitory effect is one of the mechanisms of renal anemia.