Browne P V, Shalev O, Kuypers F A, Brugnara C, Solovey A, Mohandas N, Schrier S L, Hebbel R P
Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
J Clin Invest. 1997 Sep 15;100(6):1459-64. doi: 10.1172/JCI119666.
Abnormal deposits of free iron are found on the cytoplasmic surface of red blood cell (RBC) membranes in beta-thalassemia. To test the hypothesis that this is of importance to RBC pathobiology, we administered the iron chelator deferiprone (L1) intraperitoneally to beta-thalassemic mice for 4 wk and then studied RBC survival and membrane characteristics. L1 therapy decreased membrane free iron by 50% (P = 0.04) and concomitantly improved oxidation of membrane proteins (P = 0.007), the proportion of RBC gilded with immunoglobulin (P = 0.001), RBC potassium content (P < 0.001), and mean corpuscular volume (P < 0.001). Osmotic gradient ektacytometry confirmed a trend toward improvement of RBC hydration status. As determined by clearance of RBC biotinylated in vivo, RBC survival also was significantly improved in L1-treated mice compared with controls (P = 0.007). Thus, in vivo therapy with L1 removes pathologic free iron deposits from RBC membranes in murine thalassemia, and causes improvement in membrane function and RBC survival. This result provides in vivo confirmation that abnormal membrane free iron deposits contribute to the pathobiology of thalassemic RBC.
在β地中海贫血患者的红细胞（RBC）膜细胞质表面发现游离铁异常沉积。为了验证这对RBC病理生物学具有重要意义这一假设，我们给β地中海贫血小鼠腹腔注射铁螯合剂去铁酮（L1），持续4周，然后研究RBC存活情况和膜特性。L1治疗使膜游离铁减少了50%（P = 0.04），同时改善了膜蛋白的氧化（P = 0.007）、被免疫球蛋白包被的RBC比例（P = 0.001）、RBC钾含量（P < 0.001）和平均红细胞体积（P < 0.001）。渗透梯度血细胞比容法证实RBC水合状态有改善趋势。通过体内生物素化RBC的清除率测定，与对照组相比，L1治疗组小鼠的RBC存活也显著改善（P = 0.007）。因此，L1的体内治疗可清除小鼠地中海贫血RBC膜上的病理性游离铁沉积，并改善膜功能和RBC存活。这一结果在体内证实了异常的膜游离铁沉积促成了地中海贫血RBC的病理生物学过程。
