Belanger Andrea M, Keggi Christian, Kanias Tamir, Gladwin Mark T, Kim-Shapiro Daniel B
Department of Physics.
Heart, Lung, Blood and Vascular Medicine Institute.
Transfusion. 2015 Oct;55(10):2464-72. doi: 10.1111/trf.13134. Epub 2015 Apr 23.
Sickle cell disease (SCD) is characterized by hemoglobin polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel, which dehydrates the cells leading to increased polymerization. In this study the effects of nitric oxide (NO) and its congeners on RBC deformability were examined, focusing on sickle RBCs (sRBCs).
RBCs from patients with SCD and from nonpatients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sRBCs. Deformability was measured by laser-assisted osmotic gradient ektacytometry.
Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal RBCs, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sRBCs, SNP resulted in substantial improvements in deformability (p = 0.036) and hydration (p = 0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux.
These data suggest that SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease.
镰状细胞病（SCD）的特征是脱氧时血红蛋白发生聚合。聚合导致镰状细胞变硬且变形（镰变）。红细胞（RBC）脱水会大大增加聚合反应。镰变和去镰变循环导致钙内流，进而通过钙激活的加尔多斯通道导致钾流失，使细胞脱水，导致聚合反应增加。在本研究中，研究了一氧化氮（NO）及其同类物对红细胞变形性的影响，重点是镰状红细胞（sRBCs）。
将SCD患者和非患者的红细胞暴露于各种释放NO或其同类物的化合物中。使用钙离子载体或改变sRBCs的氧张力来增加细胞内钙含量。通过激光辅助渗透梯度血细胞变形性测定法测量变形性。
与之前的一份报告一致，发现硝普钠（SNP）可防止正常红细胞因钙诱导的变形性丧失，但（与之前的一些报告相反）在未诱导钙内流时，未观察到任何NO供体有作用。重要的是，在sRBCs脱氧诱导脱水的研究中，SNP使变形性（p = 0.036）和水合作用（p = 0.024）有显著改善。亚硝酸钠呈现类似趋势。结果表明SNP对钙内流无影响，但可减少钾外流。
这些数据表明，SNP以及可能某些氮氧化物（如亚硝酸盐）可抑制加尔多斯通道，或许能够保护镰状细胞免于脱水，从而改善该病的预后。
