Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine
Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine
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DOI：
10.1038/ki.1997.393
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发表时间：
1997-09-01
影响因子：
19.6
通讯作者：
Koomans, HA
中科院分区：
文献类型：
--
作者：
Joles, JA;WillekesKoolschijn, N;Koomans, HA
白蛋白缺乏伴随着红细胞变形能力的降低和血液高粘度。白蛋白缺乏会增加血浆纤维蛋白原和甘油三酯水平，并可能改变红细胞膜脂质组成。这些选择都可能有助于降低红细胞变形性 (RCD) 和高粘滞度，在 Nagase 无白蛋白血症大鼠 (NAR) 中进行了研究，NAR 是一种突变型 Sprague Dawley 大鼠 (CON)，其特征是总蛋白水平正常，白蛋白绝对缺乏，但非白蛋白蛋白水平升高和高脂血症。极性磷脂溶血磷脂酰胆碱（LPC）的血浆蛋白结合显着降低。 LPC 仅占血浆总磷脂的 26 +/- 1%，而 CON 中则为 42 +/- 2%。 CON 血浆中的 NAR 红细胞的粘度与 CON 血浆中的 CON 红细胞相似。相反，与 CON 血浆中的 CON 红细胞相比，NAR 血浆中的 CON 红细胞显示出增加的粘度。与 CON 血浆中的 NAR 或 CON 细胞相比，NAR 血浆中的浴 NAR 和 CON 红细胞的最大变形指数显着降低（分别为 0.04 +/- 0.03 和 0.02 +/- 0.02 vs. 0.22 +/- 0.06 和 0.15 +/- 0.04；P < 0.05）。因此，血浆成分会导致 NAR 中的高粘滞血症并降低 RCD。纤维蛋白原不负责，因为血清中的红细胞和血浆中的红细胞具有相似的粘度，并且 NAR 和 CON 之间的粘度和 RCD 存在差异。血浆甘油三酯也不负有责任，因为甘油三酯减少 50% 后，血清中红细胞的粘度并未降低。 NAR 中红细胞中的 LPC 水平增加（总磷脂的 8.7 +/- 0.2 与 5.5 +/- 0.3%；P < 0.01）。向 NAR 血液中添加白蛋白会剂量依赖性地降低全血粘度，尽管血浆粘度显着增加，并且 NAR 细胞的 RCD 增加（从 0.04 +/- 0.03 到 0.21 +/- 0.01；P < 0.05）。除了 CON 血液之外，类似白蛋白对 CON RCD 也有一定影响（从 0.15 +/- 0.04 到 0.29 +/- 0.03；P < 0.05）。在 NAR 血液中添加白蛋白以剂量依赖性方式降低红细胞 LPC 含量并增加血浆 LPC 含量，而在 CON 血液中添加白蛋白仅产生轻微影响。红细胞 LPC 与红细胞膜中的其他极性磷脂之间存在相互关系，这可能表明存在交换。在CON血浆中添加LPC对NAR或CON细胞的最大变形指数没有太大影响（NAR，从0.22+/-0.06到0.18+/-0.10；CON，从0.15+/-0.04到0.12+/-0.05；NS），而在NAR血浆中添加LPC导致红细胞变得僵硬。与向 CON 血浆中的 CON 红细胞添加 LPC（从 5.6 +/- 0.4 到 6.4 +/- 0.8%；NS）相比，向 NAR 血浆中的 CON 红细胞添加 LPC 导致相对 LPC 含量增加（从 6.6 +/- 0.7 到 10.9 +/- 0.9%；P < 0.05）。因此，在缺乏白蛋白的情况下，红细胞中的LPC会增加。后者的结果是，RCD 降低并且全血粘度增加。在确定血液高粘度和 NAR 中 RCD 降低方面，红细胞磷脂的变化比血浆纤维蛋白原或甘油三酯的增加重要得多。
Albumin deficiency is accompanied by a reduction in red cell deformability and blood hyperviscosity. Albumin deficiency increases plasma fibrinogen and triglyceride levels and may alter red cell membrane lipid composition. These options, which could all contribute to reduced red cell deformability (RCD) and hyperviscosity, were studied in the Nagase analbuminemic rat (NAR), a mutant Sprague Dawley rat (CON), characterized by normal total protein levels, with an absolute deficiency of albumin, but elevated levels of non-albumin proteins and hyperlipidemia. Plasma protein-binding of the polar phopholipid lysophosphatidylcholine (LPC) was markedly decreased. LPC comprised only 26 +/- 1% of total plasma phospholipids as compared to 42 +/- 2% in CON. NAR red cells in CON plasma had a viscosity that was similar to CON red cells in CON plasma. Conversely, CON red cells in NAR plasma show an increased viscosity as compared to CON red cells in CON plasma. The maximum deformation index of bath NAR and CON red cells was markedly decreased in NAR plasma as compared to either NAR or CON cells in CON plasma (0.04 +/- 0.03 and 0.02 +/- 0.02 vs. 0.22 +/- 0.06 and 0.15 +/- 0.04, respectively; P < 0.05). Thus, plasma composition causes hyperviscosity and reduced RCD in NAR. Fibrinogen is not responsible since red cells in serum and red cells in plasma had a similar viscosity and differences in viscosity and RCD between NAR and CON were maintained. Plasma triglycerides are also not responsible since the viscosity of red cells in serum with a 50% reduction in triglycerides was not reduced. LPC levels in red cells were increased in NAR (8.7 +/- 0.2 vs. 5.5 +/- 0.3% of total phospholipids; P < 0.01). Adding albumin to NAR blood dose-dependently decreased whole blood viscosity, despite marked increases in plasma viscosity, and increased RCD of NAR cells (from 0.04 +/- 0.03 to 0.21 +/- 0.01; P < 0.05). There was also some effect on CON RCD of similar albumin addition to CON blood (from 0.15 +/- 0.04 to 0.29 +/- 0.03; P < 0.05). Adding albumin to NAR blood reduced red cell LPC content and increased plasma LPC content in a dose-dependent fashion, whereas there were only slight effects of adding albumin to CON blood. There was a reciprocal relation between red cell LPC and the other polar phospholipids in the red cell membrane, probably indicating exchange. The maximum deformability index of either NAR or CON cells was not affected much by adding LPC to CON plasma (NAR, from 0.22 +/- 0.06 to 0.18 +/- 0.10; CON, from 0.15 +/- 0.04 to 0.12 +/- 0.05; NS), whereas adding LPC to NAR plasma caused the red cells to become rigid. Adding LPC to CON red cells in NAR plasma caused a much stronger increase in relative LPC content (from 6.6 +/- 0.7 to 10.9 +/- 0.9%; P < 0.05) than adding LPC to CON red cells in CON plasma (from 5.6 +/- 0.4 to 6.4 +/- 0.8%; NS). Thus, in the absence of albumin, LPC in red blood cells is increased. As a consequence of the latter, RCD is decreased and whole blood viscosity increased. Alterations in red cell phospholipids are far more important than increases in plasma fibrinogen or triglycerides in determining hyperviscosity of blood and reduced RCD in NAR.