Zhang R L, Chopp M, Zhang Z G, Phillips M L, Rosenbloom C L, Cruz R, Manning A
Neurology Department, Henry Ford Health Sciences Center, Detroit, Michigan, USA.
J Cereb Blood Flow Metab. 1996 Nov;16(6):1126-36. doi: 10.1097/00004647-199611000-00006.
The selectin family of glycoproteins facilitates the early phase of polymorphonuclear leukocyte adhesion to the endothelial cell and, thus, may promote ischemic cell damage. To evaluate E-selectin in the pathogenesis of focal cerebral ischemia and reperfusion injury, we cloned rat E-selectin cDNA and measured the temporal profiles E-selectin mRNA (Northern blot) and protein (immunohistochemistry) during (1 h of ischemia) and after (up to 1 week) transient (2 h) middle cerebral artery (MCA) occlusion in the male Wistar rat. We also tested the effect on these rats of administration of CY-1503, an analog of sialyl Lewis(x) (SLe(x)), on ischemia cell damage. mRNA for E-selectin was first detected in the ischemic hemisphere at 2 h of reperfusion and persisted to 46 h of reperfusion. E-selectin (protein) was localized to microvessels within the ischemic lesion at 0 h of reperfusion and persisted to 70 h of reperfusion. Treatment of the ischemic animals with CY-1503 (50 mg/kg) (n = 8) significantly reduced infarct volume by 42% (p < 0.05) and significantly reduced myeloperoxidase immunoreactive cells in the ischemic lesion by 60% (p < 0.05). These findings provide the first direct evidence for the involvement of E-selectin in transient MCA occlusion in rats and suggest that the E-selectin may facilitate neutrophil adhesion and subsequent cerebral ischemic cell damage.
糖蛋白选择素家族促进多形核白细胞与内皮细胞黏附的早期阶段，因此可能会促进缺血性细胞损伤。为了评估E-选择素在局灶性脑缺血和再灌注损伤发病机制中的作用，我们克隆了大鼠E-选择素cDNA，并检测了雄性Wistar大鼠在短暂（2小时）大脑中动脉（MCA）闭塞期间（缺血1小时）和之后（长达1周）E-选择素mRNA（Northern印迹法）和蛋白（免疫组织化学）的时间变化情况。我们还测试了唾液酸化路易斯x（SLe(x)）类似物CY-1503对这些大鼠缺血性细胞损伤的影响。E-选择素mRNA在再灌注2小时时首次在缺血半球中检测到，并持续到再灌注46小时。E-选择素（蛋白）在再灌注0小时时定位于缺血病变内的微血管，并持续到再灌注70小时。用CY-1503（50 mg/kg）治疗缺血动物（n = 8）可使梗死体积显著减少42%（p < 0.05），并使缺血病变中髓过氧化物酶免疫反应性细胞显著减少60%（p < 0.05）。这些发现为E-选择素参与大鼠短暂性MCA闭塞提供了首个直接证据，并表明E-选择素可能促进中性粒细胞黏附及随后的脑缺血性细胞损伤。
