Neuroprotective effect of cilostazol against retinal ischemic damage via inhibition of leukocyte-endothelial cell interactions
Neuroprotective effect of cilostazol against retinal ischemic damage via inhibition of leukocyte-endothelial cell interactions
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DOI：
10.1111/j.1538-7836.2007.02425.x
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发表时间：
2007-04-01
影响因子：
10.4
通讯作者：
Yoshimura, N.
中科院分区：
文献类型：
--
作者：
Iwama, D.;Miyamoto, K.;Yoshimura, N.
背景：西洛他唑是一种选择性血小板磷酸二酯酶抑制剂，已被证明可减轻短暂性脑缺血后的神经元损伤。它的神经保护作用被认为是由抗血小板功能引起的。本研究旨在评价西洛他唑对视网膜缺血性损伤的抑制作用，重点是白细胞-内皮细胞相互作用。方法：采用视神经鞘暂时结扎法，造成144只雄性SD大鼠视网膜缺血60 min。在缺血诱导前给予西洛他唑。视网膜微循环中的白细胞行为在体内用扫描激光检眼镜和离体用荧光显微镜进行评价。视网膜表达的P-选择素，细胞内粘附分子-1（ICAM-1），血管内皮生长因子进行了评价，通过实时定量逆转录聚合酶链反应。组织学评价缺血诱导的视网膜损伤。结果如下：西洛他唑治疗显著抑制白细胞-内皮细胞相互作用，缺血后12小时滚动白细胞的最大数量减少了77.6%（P < 0.01）。缺血24 h后，西洛他唑对白细胞的粘附和聚集也有抑制作用（分别为36.1%和20.4%，P < 0.01）。西洛他唑组P-选择素和ICAM-1 mRNA表达明显降低（P < 0.05）。视网膜组织学检查显示西洛他唑对缺血性视网膜损伤有明显的保护作用（P < 0.01）。结论：目前的研究表明，西洛他唑通过抑制白细胞-内皮细胞相互作用减轻短暂缺血后的视网膜损伤。这种对缺血后白细胞-内皮细胞相互作用的抑制作用可能部分有助于其神经保护作用。
Background: Cilostazol, a selective platelet phosphodiesterase inhibitor, has been shown to reduce neuronal injury after transient cerebral ischemia. Its neuroprotective effect is thought to result from an antiplatelet function. This study was designed to evaluate the inhibitory effects of cilostazol against retinal ischemic damage focusing on leukocyte-endothelial cell interactions. Methods: Retinal ischemia was induced for 60 min in male Sprague-Dawley rats (n = 144) by temporary ligation of the optic sheath. Cilostazol was administered just before ischemia induction. Leukocyte behavior in the retinal microcirculation was evaluated in vivo with scanning laser ophthalmoscopy and ex vivo with fluorescence microscopy. Retinal expression of P-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor were evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction. Ischemia-induced retinal damage was evaluated histologically. Results: Treatment with cilostazol significantly suppressed leukocyte-endothelial cell interactions; the maximal numbers of rolling leukocytes were reduced by 77.6% (P < 0.01) 12 h after ischemia. Twenty-four hours after ischemia, adherent and accumulated leukocytes were also suppressed by treatment with cilostazol (36.1% and 20.4% respectively, P < 0.01). The expressions of P-selectin and ICAM-1 mRNA were suppressed significantly in cilostazol-treated retinas (P < 0.05). The retinal histological examination demonstrated a significant protective effect of cilostazol against ischemia-induced retinal damage (P < 0.01). Conclusions: The present study demonstrates that cilostazol attenuates retinal injury after transient ischemia via inhibition of leukocyte-endothelial cell interactions. This inhibitory effect on postischemic leukocyte-endothelial cell interactions might partially contribute to its neuroprotective effects.