TRANSPORT OF [I-125] TRANSFERRIN THROUGH THE RAT BLOOD-BRAIN-BARRIER
TRANSPORT OF [I-125] TRANSFERRIN THROUGH THE RAT BLOOD-BRAIN-BARRIER
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DOI：
10.1016/0006-8993(95)00363-u
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发表时间：
1995-06-19
期刊：
影响因子：
2.9
通讯作者：
PARDRIDGE, WM
中科院分区：
文献类型：
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作者：
SKARLATOS, S;YOSHIKAWA, T;PARDRIDGE, WM
转铁蛋白受体存在于脑内皮细胞的质膜中，但尚不清楚这些受体是否介导转铁蛋白通过血脑屏障的转运。本研究在氯胺酮麻醉的大鼠（250-300 g）中，通过原位脑灌注联合毛细管损耗分析和融化安装放射自显影法，评估了大鼠全转铁蛋白（rTf）在血脑屏障中的转运。[I-125]rTf以3.65 ml/min的速率经右颈内动脉输注，持续2.5 ~ 5 min。灌注5min后，[I-125]rTf在脑匀浆、血管后上清和血管小颗粒中的分布体积（volume of distribution， VD）分别为55.8 +/- 4.5、43.5 +/- 4.8和8.7 +/- 2.3 μ l/g。将[I-125]rTf与未标记的rTf或与大鼠转铁蛋白受体的高剂量OX26单克隆抗体一起输注可显著降低[I-125]rTf的转运，并且在10%大鼠血清中存在[I-125]rTf的转运几乎完全被消除。融化安装放射自显像证实了[I-125]rTf在体内通过血脑屏障的运输，在颈动脉灌注5分钟后显示银颗粒在脑实质内。这些研究与以下结论是一致的：(a)在缺乏血浆转铁蛋白竞争的情况下，[I-125]全转铁蛋白以与OX26单克隆抗体相当的速度通过血脑屏障转运；(b)检测灌注[I-125]转铁蛋白可测量运输的能力被灌注液中含有高浓度竞争转铁蛋白的大鼠血清的少量污染大大抑制。
Transferrin receptors are present in the plasma membrane of brain endothelial cells but it is unclear if these receptors mediate transport of transferrin across the blood-brain barrier (BBB). In the present study, the transport of rat holo-transferrin (rTf) across the BBB in vivo was evaluated in ketamine anesthetized rats (250-300 g) both by in situ brain perfusion coupled with capillary depletion analysis and by thaw-mount autoradiography. [I-125]rTf was infused through the right internal carotid artery at a rate of 3.65 ml/min for 2.5-5 min. After a 5 min perfusion, the volume of distribution (VD) of [I-125]rTf in the brain homogenate, the postvascular supernatant, or the vascular pellet was 55.8 +/- 4.5, 43.5 +/- 4.8, and 8.7 +/- 2.3 mu l/g, respectively. Go-infusion of [I-125]rTf with unlabeled rTf or with a high dose of OX26 monoclonal antibody to the rat transferrin receptor significantly reduced the [I-125]rTf transport, and in the presence of 10% rat serum [I-125]rTf transport was nearly entirely abolished. The transport of [I-125]rTf across the BBB in vivo was demonstrated by thaw-mount autoradiography, which showed silver grains well within brain parenchyma following a 5 min internal carotid artery perfusion. These studies are consistent with the following conclusions: (a) in the absence of competing plasma transferrin, [I-125]holotransferrin is transported through the BBB at a rate comparable to the OX26 monoclonal antibody; and (b) the ability to detect measurable transport of perfused [I-125]transferrin is greatly inhibited by a small contamination of the perfusate by rat serum, which contains high concentrations of competing transferrin.