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局部应用N-甲基-D-天冬氨酸对正常血压和高血压大鼠大脑皮质血脑屏障通透性的影响。

Effects of topical N-methyl-D-aspartate on blood-brain barrier permeability in the cerebral cortex of normotensive and hypertensive rats.

作者信息

Chi O Z, Chang Q, Weiss H R

机构信息

Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08901-1977, USA.

出版信息

Neurol Res. 1997 Oct;19(5):539-44. doi: 10.1080/01616412.1997.11740854.

DOI:10.1080/01616412.1997.11740854
PMID:9329033
Abstract

This study was performed to examine if blood-brain barrier (BBB) permeability could be increased by N-methyl-D-aspartate (NMDA) in the cerebral cortex, and to compare the degree of alteration of BBB permeability in normotensive and in chronic hypertensive rats. Twenty- to 22-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were anesthetized with isoflurane. After craniotomy in 7 animals in each group (SHR and WKY group), an NMDA patch (10 mM) was placed on one cortex (ipsilateral cortex: IC), and a normal saline patch was placed on the other cortex (control cortex: CC). The other 7 rats in each group were pretreated with MK-801 before placing NMDA and normal saline patches (SHR.MK-801 and WKY.MK-801 group). The BBB transfer coefficient (Ki) was determined using 14C-alpha-aminoisobutyric acid. The mean arterial pressures of the SHR and the SHR.MK-801 group were about 65% higher than those of the WKY and the WKY.MK-801 groups. In the WKY group, the Ki of the IC was significantly higher than that of the CC (IC: 10.0 +/- 2.7, CC: 6.2 +/- 2.4 microliters g-1 min-1). In the WKY.MK-801 group, the Ki was similar in both cortices (IC: 8.6 +/- 4.0, CC: 8.2 +/- 3.3). In the SHR group, the Ki of the IC was significantly higher than that of the CC (IC: 9.5 +/- 3.7, CC: 6.5 +/- 3.4), and the Ki of each cortex was similar to that of the corresponding cortex of the WKY group. In the SHR.MK-801 group, the Ki was similar in both cortices (IC: 7.2 +/- 1.5, CC: 7.1 +/- 2.7), and was also similar to those of the WKY.MK-801 group. Our data suggest that NMDA is involved in increasing BBB permeability. In chronic hypertension, the response of the BBB to NMDA is not altered when compared with normotension.

摘要

本研究旨在检测N-甲基-D-天冬氨酸(NMDA)是否能增加大脑皮质的血脑屏障(BBB)通透性,并比较正常血压大鼠和慢性高血压大鼠血脑屏障通透性的改变程度。选用20至22周龄的自发性高血压大鼠(SHR)和Wistar Kyoto大鼠(WKY),用异氟烷麻醉。每组7只动物(SHR组和WKY组)开颅后,在一侧大脑皮质(同侧皮质:IC)放置NMDA贴片(10 mM),另一侧大脑皮质(对照皮质:CC)放置生理盐水贴片。每组另外7只大鼠在放置NMDA和生理盐水贴片前用MK-801预处理(SHR.MK-801组和WKY.MK-801组)。使用14C-α-氨基异丁酸测定血脑屏障转运系数(Ki)。SHR组和SHR.MK-801组的平均动脉压比WKY组和WKY.MK-801组高约65%。在WKY组中,IC的Ki显著高于CC(IC:10.0±2.7,CC:6.2±2.4微升·克-1·分钟-1)。在WKY.MK-801组中,两个皮质的Ki相似(IC:8.6±4.0,CC:8.2±3.3)。在SHR组中,IC的Ki显著高于CC(IC:9.5±3.7,CC:6.5±3.4),且每个皮质的Ki与WKY组相应皮质的Ki相似。在SHR.MK-801组中,两个皮质的Ki相似(IC:7.2±1.5,CC:7.1±2.7),且也与WKY.MK-801组的Ki相似。我们的数据表明,NMDA参与增加血脑屏障通透性。与正常血压相比,慢性高血压时血脑屏障对NMDA的反应未改变。

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