肿瘤坏死因子结合蛋白对局灶性脑缺血的神经保护作用

Neuroprotective effects of TNF binding protein in focal cerebral ischemia.

作者信息

Nawashiro H, Martin D, Hallenbeck J M

机构信息

Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4128, USA.

出版信息

Brain Res. 1997 Dec 19;778(2):265-71. doi: 10.1016/s0006-8993(97)00981-5.

DOI:10.1016/s0006-8993(97)00981-5

PMID:9459543

Abstract

The effect of tumor necrosis factor binding protein (TNFbp) was studied in mice subjected to a permanent middle cerebral artery occlusion (MCAO). TNFbp is a dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp), and binds and inhibits TNF-alpha. TNFbp produced a significant reduction in the cortical infarct volume (22.6 +/- 3.5 mm3 immediately after MCAO; 25.2 +/- 2.4 mm3 1 h after MCAO) compared with vehicle-treated animals (30.3 +/- 3.7 mm3 immediately post MCAO; 31 +/- 3.7 mm3 1 h after MCAO (mean +/- S.D.) when administered intracranially up to 60 min post-occlusion. The neuroprotective effect of TNFbp was sustained in mice for 2 weeks after MCAO. DNA fragmentation at the margin of the cortical infarcts was dramatically reduced in mice treated with TNFbp whereas all control animals showed consistent and obvious DNA fragmentation 2 weeks after MCAO. TNFbp could have therapeutic value for the treatment of ischemic stroke if the problem of delivery to brain can be overcome.

摘要

在永久性大脑中动脉闭塞（MCAO）的小鼠中研究了肿瘤坏死因子结合蛋白（TNFbp）的作用。TNFbp是与聚乙二醇连接的I型可溶性TNF受体的二聚体形式（TNFbp），可结合并抑制TNF-α。与载体处理的动物相比（MCAO后立即为30.3±3.7 mm3；MCAO后1小时为31±3.7 mm3（平均值±标准差）），当在闭塞后60分钟内颅内给药时，TNFbp使皮质梗死体积显著减小（MCAO后立即为22.6±3.5 mm3；MCAO后1小时为25.2±2.4 mm3）。TNFbp的神经保护作用在MCAO后的小鼠中持续2周。在用TNFbp处理的小鼠中，皮质梗死边缘的DNA片段化显著减少，而所有对照动物在MCAO后2周均显示出一致且明显的DNA片段化。如果能够克服向大脑递送的问题，TNFbp可能对缺血性中风的治疗具有治疗价值。