Objective: To understand the effect of sirolimus on the erythropoiesis of K562 cell line and bone marrow cells from pure red cell aplasia (PRCA) patients and normal controls. Methods: Different concentrations (10, 100, 1 000 nmol/L) of sirolimus were added to the K562 cell line or bone marrow cells from PRCA patients or normal controls and cultured 14 days for BFU-E formation. Meanwhile, sirolimus was also added to the serum treated PRCA bone marrow cells to cultivate for the same priod of time. Results: Neither K562 cells, bone marrow cells from PRCA patients or normal controls showed any difference when sirolimus was added to the culture system for BFU-E. However, BFU-E formation decreased after serum was added in PRCA patients (76.40±22.48 vs 136.33±12.58, t=-4.329, P=0.001) and this suppression of BFU-E was partly corrected by 1 000 nmol/L sirolimus treatment (97.14±15.83 vs 76.40±22.48, P=0.038). Conclusions: Sirolimus may modulate the suppression of erythropoiesis by serum instead of directly stimulate the growth of red blood cells in PRCA patients.
目的： 明确西罗莫司体外对K562细胞系、获得性纯红细胞再生障碍（PRCA）患者骨髓单个核细胞向红细胞分化的影响。 方法： 以K562细胞系及治疗前PRCA患者、正常对照的骨髓单个核细胞为研究对象，采用红系甲基纤维素培养基诱导其向红系分化，观察10、100、1 000 nmol/L西罗莫司对红细胞分化的影响。并进一步在PRCA原代细胞的培养体系中加入患者自身血清，观察各组红系爆式集落形成单位（BFU-E）的变化。 结果： 不同浓度梯度西罗莫司对K562细胞系血红蛋白生成及红系表面抗原表达无明显影响；无论在正常对照还是PRCA患者骨髓单个核细胞中，西罗莫司处理组与未加药物的对照组比较，BFU-E差异无统计学意义；PRCA患者细胞加入自身血清后，其BFU-E较未加血清者明显减少[（76.40±22.48）个对（136.33±12.58）个，t=-4.329，P=0.001]，且患者细胞+自身血清+1 000 nmol/L西罗莫司组BFU-E[（97.14±15.83）个]明显高于患者细胞+自身血清组（P=0.038）。 结论： 西罗莫司可能无直接刺激红细胞生长和分化作用，但可以拮抗患者血清对红细胞的抑制作用，可能通过抑制血清中的成分而起作用。.
Keywords: Erythroid-burst forming unit; K562 cells; Pure red cell aplasia; Serum; Sirolimus.