Briehl R W
Blood Cells. 1982;8(2):201-12.
Intraerythrocytic gelation of deoxyhemoglobin S is the immediate cause of red cell deformation and rigidification in sickle cell disease. Hence the rheology of hemoglobin S gels, heretofore little studied, plays a central role in pathogenesis. I have shown previously [2] that unsheared gels are solid-like whereas sheared gels are viscous in character. In the present studies the delay (nucleation) time for gelation (after a temperature jump) was examined in the absence and presence of shear, employing a sharp rise in viscosity as the end point of the delay time. Shearing rates in the range from 1.92 to 384 s-1 progressively accelerate the delay time. In another series of experiments the temperature jump was carried out in the absence of shear, shear being instituted later in the delay period. There was a sparing effect of the time of incubation in the absence of shear on the subsequent time under shear needed to induce gelation. A linear relation was observed between these two parameters, indicating that shear operates with constant efficacy in accelerating gelation, independent of when in the delay time it is applied. This suggests that the mechanism of assembly is the same throughout the period. Since shear probably operates through the breakage of fibers with the creation of new growth centers, the results also suggest that long, breakable, fibers are present even relatively early in the delay period. Values were obtained for delay time under shear and (by extrapolation) delay time under no shear. The temperature dependence (and hence apparent activation energy) of the latter is larger than that of the former; i.e. the effect of shear in shortening delay time is more marked as temperatures are lowered. With respect to pathogenesis, these results suggest that intraerythrocytic shearing may be detrimental because it accelerates gelation. On the other hand shearing of gels converts them from solid-like to viscous, and hence more deformable, systems; this effect of shear might be expected to ameliorate pathogenesis. Consequently, the pathogenic effects of intraerythrocytic shearing may depend on when the shear is applied.
脱氧血红蛋白S在红细胞内形成凝胶是镰状细胞病中红细胞变形和僵化的直接原因。因此，此前鲜有研究的血红蛋白S凝胶的流变学在发病机制中起着核心作用。我之前已经表明[2]，未剪切的凝胶呈固体状，而剪切后的凝胶具有粘性。在本研究中，在有剪切和无剪切的情况下，通过粘度的急剧上升作为延迟时间的终点，检测了凝胶化的延迟（成核）时间（温度跃升后）。剪切速率在1.92至384 s-1范围内会逐渐延长延迟时间。在另一系列实验中，在无剪切的情况下进行温度跃升，在延迟期后期施加剪切。在无剪切情况下的孵育时间对随后在剪切下诱导凝胶化所需时间有一定的节省作用。观察到这两个参数之间存在线性关系，表明剪切在加速凝胶化方面具有恒定的效力，与在延迟时间的何时应用无关。这表明组装机制在整个过程中是相同的。由于剪切可能通过纤维断裂并产生新的生长中心起作用，结果还表明即使在延迟期相对较早的时候也存在长的、易断裂的纤维。获得了剪切下的延迟时间值以及（通过外推）无剪切下的延迟时间值。后者的温度依赖性（以及表观活化能）大于前者；即随着温度降低，剪切在缩短延迟时间方面的作用更为明显。关于发病机制，这些结果表明红细胞内剪切可能是有害的，因为它加速了凝胶化。另一方面，凝胶的剪切将它们从固体状转变为粘性，因此更易变形的系统；剪切的这种作用可能会改善发病机制。因此，红细胞内剪切的致病作用可能取决于剪切的施加时间。
