聚乙二醇超氧化物歧化酶和过氧化氢酶可减轻仔猪缺血后血脑屏障通透性的增加。

Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets.

作者信息

Armstead W M, Mirro R, Thelin O P, Shibata M, Zuckerman S L, Shanklin D R, Busija D W, Leffler C W

机构信息

Department of Physiology, University of Tennessee, Memphis 38163.

出版信息

Stroke. 1992 May;23(5):755-62. doi: 10.1161/01.str.23.5.755.

DOI:10.1161/01.str.23.5.755

PMID:1579974

Abstract

BACKGROUND AND PURPOSE

Transport of urea across the blood-brain barrier is increased during postischemic cerebral reperfusion in the piglet. Ischemia/reperfusion also has been observed to increase apparent superoxide anion generation on the surface of the brain. The present study was designed to address the hypothesis that the increased transfer of urea into the brain after ischemia/reperfusion could be due to superoxide anion-induced alterations in blood-brain barrier permeability.

METHODS

Blood-to-brain transfer of carbon-14-labeled urea was measured in four groups (n = 7 each) of newborn pigs: 1) control (no ischemia, no pretreatment), 2) pretreatment with polyethylene glycol superoxide dismutase (1,000 IU/kg) and polyethylene glycol catalase (10,000 IU/kg i.v.) but no ischemia, 3) no pretreatment and 20 minutes of ischemia followed by 2 hours of reperfusion, and 4) pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase in addition to ischemia/reperfusion. The following brain regions were investigated: cerebrum, caudate, midbrain, pons, medulla, and cerebellum.

RESULTS

Polyethylene glycol superoxide dismutase inhibited generation of superoxide anion by the brain during reperfusion after ischemia. Regional transfer of [14C]urea from blood to brain increased at 2 hours' reperfusion. This ischemia-induced increase in blood-to-brain transfer of [14C]urea was attenuated by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase: e.g., cerebrum Kin was 28 +/- 2 in the control group, 26 +/- 3 in the pretreated/no ischemia group, 67 +/- 5 in the untreated/ischemia group, and 40 +/- 2 ml.g-1.s-1.10(6) in the pretreated/ischemia group. After ischemia/reperfusion, cerebral blood flow was unchanged by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase.

CONCLUSIONS

These data suggest that production of a partially reduced species of oxygen contributes to the increased urea transfer across the blood-brain barrier after ischemia in the newborn pig.

摘要

背景与目的

仔猪脑缺血后再灌注期间，尿素穿过血脑屏障的转运增加。缺血/再灌注还可观察到脑表面超氧阴离子生成增加。本研究旨在验证如下假说：缺血/再灌注后尿素向脑内转运增加可能是由于超氧阴离子诱导血脑屏障通透性改变所致。

方法

将新生猪分为四组（每组n = 7），测量碳 - 14标记尿素的血脑转运情况：1）对照组（无缺血，未预处理）；2）用聚乙二醇超氧化物歧化酶（1000 IU/kg）和聚乙二醇过氧化氢酶（10000 IU/kg静脉注射）预处理但无缺血；3）未预处理，缺血20分钟后再灌注2小时；4）除缺血/再灌注外，还用聚乙二醇超氧化物歧化酶和聚乙二醇过氧化氢酶预处理。研究的脑区包括：大脑、尾状核、中脑、脑桥、延髓和小脑。

结果

聚乙二醇超氧化物歧化酶抑制缺血后再灌注期间脑内超氧阴离子的生成。再灌注2小时时，[14C]尿素从血到脑的区域转运增加。聚乙二醇超氧化物歧化酶和聚乙二醇过氧化氢酶预处理可减轻缺血诱导的[14C]尿素血脑转运增加：例如，对照组大脑的Kin为28±2，预处理/无缺血组为26±3，未处理/缺血组为67±5，预处理/缺血组为40±2 ml·g-1·s-1·10(6)。缺血/再灌注后，聚乙二醇超氧化物歧化酶和聚乙二醇过氧化氢酶预处理对脑血流量无影响。