Yanaka K, Spellman S R, McCarthy J B, Oegema T R, Low W C, Camarata P J
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, USA.
J Neurosurg. 1996 Dec;85(6):1102-7. doi: 10.3171/jns.1996.85.6.1102.
Heparin has long been established as an anticoagulant. Although heparin has been demonstrated to reduce brain injury after ischemia and reperfusion, its mechanism of action remains unknown. Recent investigations reveal that it can modulate biological processes such as binding to adhesion receptors on endothelial cells and leukocytes. The authors hypothesized that heparin's protective effect is closely related to its antileukocyte adherence property. They evaluated the efficacy of sulfated polysaccharides (unfractionated heparin, low-molecular-weight heparin, heparan sulfate, chondroitin sulfate C, and dextran sulfate) on leukocyte accumulation, infarction size, and neurological outcome after transient focal cerebral ischemia in rats subjected to 1 hour of ischemia and 48 hours of reperfusion. Forty-nine animals were included in the study. The animals receiving unfractionated heparin or dextran sulfate showed a significant reduction in leukocyte accumulation, infarct size, and neurological dysfunction 48 hours after reperfusion (p < 0.05) when compared to untreated animals. The animals receiving unfractionated heparin also showed significantly better results than the animals receiving an equivalent anticoagulant dose of low-molecular-weight heparin. These data indicate that heparin's antileukocyte property plays a more important role than its anticoagulant ability in neuronal protection. The relative potency of the sulfated polysaccharides tested in leukocyte depletion was closely related to their degree of sulfation. Thus, in addition to demonstrating the potential efficacy of heparin as a therapeutic agent for ischemia and reperfusion injury by the prevention of leukocyte accumulation, the results also serve as a basis for studying important cellular and molecular events that contribute to tissue damage.
肝素长期以来一直被用作抗凝剂。尽管肝素已被证明可减少缺血再灌注后的脑损伤，但其作用机制仍不清楚。最近的研究表明，它可以调节生物过程，如与内皮细胞和白细胞上的黏附受体结合。作者推测，肝素的保护作用与其抗白细胞黏附特性密切相关。他们评估了硫酸化多糖（普通肝素、低分子量肝素、硫酸乙酰肝素、硫酸软骨素C和硫酸葡聚糖）对短暂局灶性脑缺血大鼠（缺血1小时，再灌注48小时）白细胞聚集、梗死面积和神经功能结局的影响。该研究纳入了49只动物。与未治疗的动物相比，接受普通肝素或硫酸葡聚糖的动物在再灌注48小时后白细胞聚集、梗死面积和神经功能障碍显著减少（p<0.05）。接受普通肝素的动物也比接受同等抗凝剂量低分子量肝素的动物表现出明显更好的结果。这些数据表明，肝素的抗白细胞特性在神经元保护中比其抗凝能力发挥更重要的作用。所测试的硫酸化多糖在白细胞消耗方面的相对效力与其硫酸化程度密切相关。因此，这些结果除了证明肝素作为一种通过预防白细胞聚集治疗缺血再灌注损伤的治疗剂的潜在疗效外，还为研究导致组织损伤的重要细胞和分子事件提供了基础。
