Yanaka K, Camarata P J, Spellman S R, McCarthy J B, Furcht L T, Low W C, Heros R C
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, USA.
J Neurosurg. 1996 Jul;85(1):125-30. doi: 10.3171/jns.1996.85.1.0125.
Leukocytes play an important role in the development of ischemia-reperfusion injury. This study was conducted to ascertain whether synthetic peptides corresponding to the cell- and heparin-binding sequences of fibronectin that disturb leukocyte adhesion molecules were effective in neuronal protection after transient focal cerebral ischemia in rats. The authors evaluated the efficacy of peptides on infarction size, leukocyte infiltration in the ischemic tissue, and neurological outcome in rats subjected to 1 hour of cerebral ischemia and 48 hours of reperfusion. Twenty-one animals were divided into three groups: transient ischemia without treatment (Group I), transient ischemia with administration of vehicle (Group II), and transient ischemia with administration of fibronectin peptides (Group III). The mean myeloperoxidase activity (U/g wet wt) in the ischemic area was as follows: Group I, 0.19% +/- 0.05; Group II, 0.21% +/- 0.03; and Group III, 0.08% +/- 0.02. The mean size of the infarction as a percentage of the total hemispheric volume was as follows: Group I, 38.35% +/- 1.34%; Group II, 39.21% +/- 2.42%; and Group III, 25.81% +/- 4.87%. Group III showed a significant decrease in myeloperoxidase activity in the lesion and the infarction size was smaller when compared to Groups I and II (p < 0.05). The neurological grade in Group III was significantly better than in Groups I and II at 48 hours after reperfusion (p < 0.01). This study is the first to explore the therapeutic potential of synthetic fibronectin peptides in brain protection after transient focal ischemia, and the results also serve as a basis for studies of important cellular and molecular events that contribute to tissue damage.
白细胞在缺血再灌注损伤的发生发展中起重要作用。本研究旨在确定与纤连蛋白的细胞结合序列和肝素结合序列相对应的、干扰白细胞黏附分子的合成肽，在大鼠短暂性局灶性脑缺血后对神经元是否具有保护作用。作者评估了这些肽对梗死面积、缺血组织中白细胞浸润以及经历1小时脑缺血和48小时再灌注的大鼠神经功能结局的影响。21只动物被分为三组：未治疗的短暂性缺血组（I组）、给予赋形剂的短暂性缺血组（II组）和给予纤连蛋白肽的短暂性缺血组（III组）。缺血区域的平均髓过氧化物酶活性（U/g湿重）如下：I组，0.19%±0.05；II组，0.21%±0.03；III组，0.08%±0.02。梗死面积占总半球体积的百分比平均值如下：I组，38.35%±1.34%；II组，39.21%±2.42%；III组，25.81%±4.87%。与I组和II组相比，III组病变中的髓过氧化物酶活性显著降低，梗死面积更小（p<0.05）。再灌注48小时后，III组的神经功能评分显著优于I组和II组（p<0.01）。本研究首次探讨了合成纤连蛋白肽在短暂性局灶性缺血后脑保护中的治疗潜力，其结果也为研究导致组织损伤的重要细胞和分子事件提供了依据。
