Warth J A, Rucknagel D L
Prog Clin Biol Res. 1987;240:429-49.
We have conducted a series of studies using discontinuous arabinogalactan density gradient ultracentrifugation of erythrocytes from the peripheral blood of: patients with sickle cell anemia (SCA), in and out of pain crisis; hydrated SCA, hemoglobin SC, and normal individuals all of whom were pain-free; and patients with SCA given short courses of oral vasodilator compounds. Our results indicate that in pain crisis patients develop an echinocytic change that is most prominent in the denser layers (specific gravity greater than 1.128 g/ml) of the discontinuous gradient and effects both irreversibly sickled cells (ISC) and non-ISC. This echinocytic change, we have previously shown, correlates with a decrease in erythrocyte reduced glutathione, a major intraerythrocyte anti-oxidant compound. We could find no consistent change in the percentage of dense cells in pain crisis versus out of crisis. However, out of crisis, hydration led to a marked increase in the percentage of dense erythrocytes in sickle cell anemia and in a HbSC patient, compared to the same individual out of crisis and on ad lib fluids. There was no consistent change in echinocytic forms. Because hydration may be expected to have produced an increase in intravascular volume and vasodilation, we determined whether short courses of three different vasodilators would increase the dense fraction in patients with SCA who were pain-free. There was no change in percentage of dense erythrocytes or in the percentage of echinocytes. We concluded that painful crisis occurs in association with an echinocytic change that may be induced by oxidant injury and that in the pain-free state, hydration, but not short courses of vasodilator drugs, increased the percentage of dense erythrocytes but not the degree of echinocytosis they displayed. The differential effect of hydration, with respect to painful crisis, may indicate that these dense cells are bound to vascular endothelium or trapped in blood vessels at the time of crisis but mobilized by hydration in the out-of-crisis state.
我们进行了一系列研究，采用间断阿拉伯半乳聚糖密度梯度超速离心法处理以下人群外周血中的红细胞：镰状细胞贫血（SCA）患者，处于疼痛危象期和非疼痛危象期；水化的SCA患者、血红蛋白SC患者以及均无疼痛症状的正常个体；接受短期口服血管扩张剂化合物治疗的SCA患者。我们的结果表明，在疼痛危象期患者会出现棘红细胞改变，这种改变在间断梯度较密层（比重高于1.128 g/ml）最为显著，且对不可逆镰状细胞（ISC）和非ISC均有影响。我们之前已经表明，这种棘红细胞改变与红细胞还原型谷胱甘肽减少有关，还原型谷胱甘肽是红细胞内主要的抗氧化化合物。我们发现疼痛危象期与非疼痛危象期相比，致密细胞的百分比没有一致的变化。然而，在非疼痛危象期，与处于相同状态但随意饮水的个体相比，水化导致镰状细胞贫血患者和一名血红蛋白SC患者中致密红细胞的百分比显著增加。棘红细胞形态没有一致的变化。由于水化可能会使血管内容量增加并导致血管扩张，我们确定了三种不同血管扩张剂的短期疗程是否会增加无疼痛症状的SCA患者的致密部分。致密红细胞的百分比和棘红细胞的百分比均无变化。我们得出结论，疼痛危象的发生与可能由氧化损伤诱导的棘红细胞改变有关，并且在无疼痛状态下，水化而非短期血管扩张剂药物疗程会增加致密红细胞的百分比，但不会增加其显示的棘红细胞形成程度。水化对于疼痛危象的不同影响可能表明，这些致密细胞在危象期与血管内皮结合或被困在血管中，但在非危象状态下通过水化而被动员。
