Rachmilewitz Eliezer A, Weizer-Stern Orly, Adamsky Konstantin, Amariglio Ninette, Rechavi Gideon, Breda Laura, Rivella Stefano, Cabantchik Z Ioav
Department of Hematology, The Edith Wolfson Medical Center, P.O. Box 5, 58100 Holon, Israel.
Ann N Y Acad Sci. 2005;1054:118-23. doi: 10.1196/annals.1345.014.
The pathophysiology of thalassemia is, to a certain extent, associated with the generation of labile iron in the pathological red blood cell (RBC). The appearance of such forms of iron at the inner and outer cell surfaces exposes the cell to conditions whereby the labile metal promotes the formation of reactive oxygen species (ROS) leading to cumulative cell damage. Another source of iron accumulation results from increased absorption due to decreased expression of hepcidin. The presence of labile plasma iron (LPI) was carried out using fluorescent probes in the FACS. RNA expression of hepcidin was measured in two models of thalassemic mice. Hepcidin expression was also measured in human hepatoma HepG2 cells following incubation with thalassemic sera. LPI was identified and could be quantitatively measured and correlated with other parameters of iron overload. Hepcidin expression was downregulated in the livers of thalassemic mice, in major more than in intermedia. Thalassemic sera down regulated hepcidin expression in HepG2 liver cells. A possible way to decrease iron absorption could be by modulating hepcidin expression pharmacologically, by gene therapy or by its administration. Treatment with combination of antioxidants such as N-acetylcysteine for proteins and vitamin E for lipids in addition to iron chelators could neutralize the deleterious effects of ROS and monitored by quantitation of LPI.
地中海贫血的病理生理学在一定程度上与病理性红细胞（RBC）中不稳定铁的生成有关。这种形式的铁在细胞内表面和外表面的出现，使细胞处于不稳定金属促进活性氧（ROS）形成从而导致细胞累积损伤的条件下。铁积累的另一个来源是由于铁调素表达降低导致的吸收增加。使用荧光探针在流式细胞仪中检测不稳定血浆铁（LPI）的存在。在两种地中海贫血小鼠模型中测量铁调素的RNA表达。在用地中海贫血血清孵育后的人肝癌HepG2细胞中也测量了铁调素的表达。LPI被识别出来，并且可以进行定量测量，并与铁过载的其他参数相关联。在地中海贫血小鼠的肝脏中，铁调素表达下调，重型比中间型下调更明显。地中海贫血血清下调了HepG2肝细胞中铁调素的表达。降低铁吸收的一种可能方法是通过药物调节铁调素表达、基因治疗或给予铁调素。除了铁螯合剂外，用抗氧化剂如用于蛋白质的N-乙酰半胱氨酸和用于脂质的维生素E联合治疗可以中和ROS的有害作用，并通过LPI定量进行监测。
