阿加曲班可减轻短暂性视网膜缺血后白细胞与血小板-内皮细胞的相互作用。

Argatroban attenuates leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia.

作者信息

Miyahara Shinsuke, Kiryu Junichi, Tsujikawa Akitaka, Katsuta Hideto, Nishijima Kazuaki, Miyamoto Kazuaki, Yamashiro Kenji, Nonaka Atsushi, Honda Yoshihito

机构信息

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaramachi Sakyo-ku, Kyoto-shi, Kyoto, 606-8507, Japan.

出版信息

Stroke. 2003 Aug;34(8):2043-9. doi: 10.1161/01.STR.0000083052.01361.3D. Epub 2003 Jul 17.

DOI:10.1161/01.STR.0000083052.01361.3D

PMID:12869718

Abstract

BACKGROUND AND PURPOSE

Argatroban, a direct thrombin inhibitor, has been shown to reduce neural injury after transient cerebral ischemia. It has also been reported that this neuroprotective effect results from an anticoagulant function. This study was designed to evaluate quantitatively the inhibitory effects of argatroban on leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia.

METHODS

Retinal ischemia was induced for 60 minutes in male Long-Evans rats by temporary ligation of the optic sheath (n=342). Argatroban was administered just after induction of ischemia. Leukocyte and platelet behavior in the retinal microcirculation was then evaluated in vivo with scanning laser ophthalmoscopy. The expression of P-selectin and intracellular adhesion molecule-1 (ICAM-1) was evaluated by reverse transcription-polymerase chain reaction. After 10 days of reperfusion, ischemia-induced retinal damage was evaluated histologically.

RESULTS

Treatment with argatroban suppressed leukocyte-endothelial cell interactions; the maximum numbers of rolling and accumulated leukocytes were reduced by 90.1% (P<0.05) and 58.7% (P<0.05), respectively, at 12 hours after reperfusion. Treatment with argatroban also suppressed platelet-endothelial cell interactions; the maximum numbers of rolling and adhering platelets were reduced by 91.8% (P<0.01) and 78.9% (P<0.01), respectively, at 12 hours after reperfusion. The expression of P-selectin and ICAM-1 mRNA was suppressed significantly in the argatroban-treated retinas (P<0.01). Histologic examination demonstrated the protective effect of argatroban on ischemia-induced retinal damage (P<0.01).

CONCLUSIONS

Argatroban treatment suppressed leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia. This inhibitory effect on postischemic blood cell-endothelial cell interactions might partially contribute to its neuroprotective effects.

摘要

背景与目的

阿加曲班是一种直接凝血酶抑制剂，已被证明可减轻短暂性脑缺血后的神经损伤。也有报道称这种神经保护作用源于抗凝功能。本研究旨在定量评估阿加曲班对短暂性视网膜缺血后白细胞与血小板 - 内皮细胞相互作用的抑制作用。

方法

通过暂时结扎雄性Long - Evans大鼠的视神经鞘诱导视网膜缺血60分钟（n = 342）。在缺血诱导后立即给予阿加曲班。然后用扫描激光检眼镜在体内评估视网膜微循环中的白细胞和血小板行为。通过逆转录 - 聚合酶链反应评估P - 选择素和细胞间黏附分子 -1（ICAM -1）的表达。再灌注10天后，组织学评估缺血诱导的视网膜损伤。

结果

阿加曲班治疗可抑制白细胞与内皮细胞的相互作用；再灌注12小时时，滚动和聚集白细胞的最大数量分别减少了90.1%（P <0.05）和58.7%（P <0.05）。阿加曲班治疗还可抑制血小板与内皮细胞的相互作用；再灌注12小时时，滚动和黏附血小板的最大数量分别减少了91.8%（P <0.01）和78.9%（P <0.01）。在阿加曲班治疗的视网膜中，P - 选择素和ICAM -1 mRNA的表达明显受到抑制（P <0.01）。组织学检查显示阿加曲班对缺血诱导的视网膜损伤具有保护作用（P <0.01）。