Jiang N, Moyle M, Soule H R, Rote W E, Chopp M
Department of Neurology, Henry Ford Health Science Center, Detroit, MI, USA.
Ann Neurol. 1995 Dec;38(6):935-42. doi: 10.1002/ana.410380615.
We tested the neuroprotective potential of neutrophil inhibitory factor (rNIF), a novel 41-kd recombinant glycoprotein derived from a hookworm, in a model of focal cerebral ischemia in the rat. Male Wistar rats were assigned to treatment with rNIF and vehicle. Middle cerebral artery occlusion (MCAO) for 2 hours was induced by insertion of an intraluminal suture. Infusion of the drug was initiated at the onset of reperfusion. Infarct volume was determined 48 hours after reperfusion. Neutrophils were measured within the ischemic tissue by myeloperoxidase (MPO) staining. Treatment with rNIF resulted in a 48% reduction in cerebral infarction compared with control animals (p < 0.01). Neutrophil accumulation in the ischemic brains of rNIF-treated rats was reduced significantly (p < 0.01) compared with control animals. The number of neutrophils within the infarcted tissue correlated positively with the size of the area of infarction (p < 0.001, r = 0.6) within representative cerebral coronal sections. We demonstrated a significant neuroprotective effect of rNIF with continuous treatment for 48 hours following 2 hours of MCAO. The neuroprotective effect was correlated with a reduced number of neutrophils within the ischemic tissue. These results demonstrate potential therapeutic properties of rNIF in the management of stroke.
我们在大鼠局灶性脑缺血模型中测试了嗜中性粒细胞抑制因子(rNIF)的神经保护潜力,rNIF是一种源自钩虫的新型41-kd重组糖蛋白。将雄性Wistar大鼠分为rNIF治疗组和溶剂对照组。通过插入腔内缝线诱导大脑中动脉闭塞(MCAO)2小时。在再灌注开始时开始输注药物。再灌注48小时后测定梗死体积。通过髓过氧化物酶(MPO)染色测量缺血组织内的嗜中性粒细胞。与对照动物相比,rNIF治疗使脑梗死减少了48%(p < 0.01)。与对照动物相比,rNIF治疗的大鼠缺血脑中嗜中性粒细胞的积累显著减少(p < 0.01)。在代表性脑冠状切片中,梗死组织内嗜中性粒细胞的数量与梗死面积大小呈正相关(p < 0.001,r = 0.6)。我们证明了在MCAO 2小时后持续治疗48小时,rNIF具有显著的神经保护作用。这种神经保护作用与缺血组织内嗜中性粒细胞数量减少有关。这些结果证明了rNIF在中风治疗中的潜在治疗特性。