NG-硝基-L-精氨酸可延缓大鼠局灶性缺血期间脑损伤的发展。

NG-nitro-L-arginine delays the development of brain injury during focal ischemia in rats.

作者信息

Kozniewska E, Roberts T P, Tsuura M, Mintorovitch J, Moseley M E, Kucharczyk J

机构信息

Department of Radiology, University of California, San Francisco.

出版信息

Stroke. 1995 Feb;26(2):282-8; discussion 288-9. doi: 10.1161/01.str.26.2.282.

DOI:10.1161/01.str.26.2.282

PMID:7831702

Abstract

BACKGROUND AND PURPOSE

The present study was designed to determine the effect of nitro-L-arginine, the inhibitor of nitric oxide synthesis, on the evolution of cytotoxic brain edema during focal cerebral ischemia.

METHOD

Diffusion-weighted and contrast-enhanced, perfusion-sensitive magnetic resonance imaging was performed in anesthetized, mechanically ventilated rats at 30 minutes and 1, 2, and 3 hours after occlusion of the middle cerebral artery combined with coagulation of the basilar artery. At the onset of ischemia, the animals were infused intravenously with 0.5 mL of either 0.9% NaCl or nitro-L-arginine (30 mg/kg). The severity of cytotoxic edema was evaluated based on changes in the water apparent diffusion coefficient (ADC) derived from diffusion-weighted images. The size of the area affected by ischemia was evaluated 3 hours after occlusion using 2,3,5-triphenyltetrazolium chloride (TTC) staining.

RESULTS

The percentage decrease of ADC in the striatum of rats pretreated with nitro-L-arginine was significantly smaller (P < .05) than in the control group at 30 minutes and 1 and 2 hours of ischemia. The ADC in the injured cortex of nitro-L-arginine-treated rats did not differ significantly from the ADC value measured in the contralateral cortex until 3 hours after the occlusion. However, at 3 hours of ischemia the percentage decrease of ADC in both the striatum and the cortex of either group of rats was similar. This transient attenuation of ADC drop during ischemia after nitro-L-arginine pretreatment occurred concurrently with a transient improvement of blood supply to the ischemic regions. The percentage of hemispheric area with abnormal TTC staining after 3 hours of ischemia did not differ between control and nitro-L-arginine-treated rats.

CONCLUSIONS

Nitro-L-arginine delays the development of ischemic injury by retarding cytotoxic brain edema. This effect is, at least partially, mediated by an improvement in blood supply to the ischemia tissues.

摘要

背景与目的

本研究旨在确定一氧化氮合成抑制剂硝基-L-精氨酸对局灶性脑缺血期间细胞毒性脑水肿演变的影响。

方法

在麻醉、机械通气的大鼠大脑中动脉闭塞并联合基底动脉凝固后30分钟、1小时、2小时和3小时，进行扩散加权及对比增强灌注敏感磁共振成像。在缺血开始时，给动物静脉注射0.5 mL的0.9%氯化钠或硝基-L-精氨酸（30 mg/kg）。基于扩散加权图像得出的水表观扩散系数（ADC）变化评估细胞毒性水肿的严重程度。闭塞3小时后，使用2,3,5-三苯基氯化四氮唑（TTC）染色评估缺血影响区域的大小。

结果

在缺血30分钟、1小时和2小时时，用硝基-L-精氨酸预处理的大鼠纹状体中ADC的降低百分比明显小于对照组（P <.05）。在闭塞后3小时之前，用硝基-L-精氨酸处理的大鼠损伤皮质中的ADC与对侧皮质中测得的ADC值无显著差异。然而，在缺血3小时时，两组大鼠纹状体和皮质中ADC的降低百分比相似。硝基-L-精氨酸预处理后缺血期间ADC下降的这种短暂减弱与缺血区域血液供应的短暂改善同时发生。缺血3小时后，对照组和用硝基-L-精氨酸处理的大鼠之间，TTC染色异常的半球区域百分比没有差异。