缺血前而非缺血后给予锌原卟啉治疗可减小大鼠短暂局灶性脑缺血后的梗死体积并减少水肿积聚。

Preischemic but not postischemic zinc protoporphyrin treatment reduces infarct size and edema accumulation after temporary focal cerebral ischemia in rats.

作者信息

Kadoya C, Domino E F, Yang G Y, Stern J D, Betz A L

机构信息

Department of Pharmacology, University of Michigan, Ann Arbor 48109-0630, USA.

出版信息

Stroke. 1995 Jun;26(6):1035-8. doi: 10.1161/01.str.26.6.1035.

DOI:10.1161/01.str.26.6.1035

PMID:7762020

Abstract

BACKGROUND AND PURPOSE

Zinc protoporphyrin (ZnPP) has multiple actions. It is an interleukin-1 antagonist as well as a hemeoxygenase inhibitor. Interleukin-1 is produced in ischemic brain and probably contributes to ischemic injury, although the role of heme oxygenase during ischemia is unknown. Whether ZnPP treatment is more effective before or after ischemia, as well as whether it is more protective in permanent or temporary cerebral ischemia, is also unknown. Therefore, we investigated the effect of ZnPP on infarction size and edema in a rodent model of temporary and permanent focal cerebral ischemia.

METHODS

Two groups of adult male Sprague-Dawley rats were pretreated with either 50 mg/kg ZnPP IP or saline and subjected to permanent middle cerebral artery occlusion 30 minutes later. Four additional groups of animals were subjected to 2 hours of temporary middle cerebral artery occlusion followed by 22 hours of reperfusion. Two of these groups were pretreated 30 minutes before middle cerebral artery occlusion with either 50 mg/kg ZnPP IP or saline. The other groups received ZnPP at either 2 or 4 hours after middle cerebral artery occlusion. Regional cerebral blood flow in the ischemic cortex was monitored with laser Doppler flowmetry. Cerebral infarct size and brain water were measured 24 hours after the onset of either form of ischemia.

RESULTS

Regional cerebral blood flow after occlusion was approximately 13% to 20% of baseline after either permanent or temporary ischemia. ZnPP had no effect on regional cerebral blood flow, infarct size, or edema formation in permanent ischemia. In contrast, pretreatment significantly reduced infarct size (17.2 +/- 6.6% in controls versus 6.2 +/- 2.9% in pretreated rats) and edema formation (center zone, 4.00 +/- 0.71% water in controls versus 1.18 +/- 0.26% water in pretreated rats) in the model of temporary ischemia, but treatment after occlusion had no effect.

CONCLUSIONS

ZnPP treatment protected the brain when administered early in the temporary ischemia model.

摘要

背景与目的

锌原卟啉（ZnPP）具有多种作用。它是一种白细胞介素 - 1拮抗剂，也是一种血红素加氧酶抑制剂。白细胞介素 - 1在缺血性脑内产生，可能促成缺血性损伤，尽管血红素加氧酶在缺血期间的作用尚不清楚。ZnPP治疗在缺血前还是缺血后更有效，以及它在永久性或暂时性脑缺血中是否更具保护作用，也尚不清楚。因此，我们在暂时性和永久性局灶性脑缺血的啮齿动物模型中研究了ZnPP对梗死面积和水肿的影响。

方法

两组成年雄性Sprague - Dawley大鼠分别经腹腔注射50mg/kg ZnPP或生理盐水预处理，30分钟后进行永久性大脑中动脉闭塞。另外四组动物进行2小时的暂时性大脑中动脉闭塞，随后再灌注22小时。其中两组在大脑中动脉闭塞前30分钟分别经腹腔注射50mg/kg ZnPP或生理盐水预处理。其他组在大脑中动脉闭塞后2小时或4小时给予ZnPP。用激光多普勒血流仪监测缺血皮质的局部脑血流量。在任何一种缺血形式发作24小时后测量脑梗死面积和脑含水量。

结果

永久性或暂时性缺血后闭塞后脑局部血流量约为基线的13%至20%。ZnPP对永久性缺血时的局部脑血流量、梗死面积或水肿形成均无影响。相比之下，在暂时性缺血模型中，预处理显著减小了梗死面积（对照组为17.2±6.6%，预处理大鼠为6.2±2.9%）和水肿形成（中心区，对照组水含量为4.00±0.71%，预处理大鼠为1.18±0.26%），但闭塞后治疗无效。