Cilostazol, Not Aspirin, Reduces Ischemic Brain Injury via Endothelial Protection in Spontaneously Hypertensive Rats
Cilostazol, Not Aspirin, Reduces Ischemic Brain Injury via Endothelial Protection in Spontaneously Hypertensive Rats
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DOI：
10.1161/strokeaha.110.609834
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发表时间：
2011-09-01
期刊：
影响因子：
8.3
通讯作者：
Kitagawa, Kazuo
中科院分区：
文献类型：
--
作者：
Oyama, Naoki;Yagita, Yoshiki;Kitagawa, Kazuo
背景和目的：高血压导致脑动脉内皮功能障碍是公认的。最近，西洛他唑已被用于缺血性卒中的二级预防。在抗血小板药物中，磷酸二酯酶抑制剂包括西洛他唑已被证明对内皮细胞具有保护作用。本研究的目的是探讨西洛他唑和阿司匹林对自发性高血压大鼠（SHR）脑缺血后大脑皮层内皮型一氧化氮合酶（eNOS）磷酸化、内皮功能和梗死面积的影响。方法5周龄雄性SHR接受5周的含0.1%阿司匹林、0.1%西洛他唑、0.3%西洛他唑、或载体对照。Western blot检测脑皮质总eNOS蛋白和Ser（1177）-磷酸化eNOS蛋白水平。为了评估eNOS在维持脑血流量方面的贡献，我们在输注L-N-5-（1-亚氨乙基）鸟苷酸后通过激光多普勒血流仪监测脑血流量。此外，我们评估残留的微灌注荧光标记的血清蛋白和梗死面积短暂局灶性脑ischemia.Results-In SHR，血压和心率各组之间相似。西洛他唑治疗的SHR有一个显着较高的比例磷酸eNOS/总eNOS蛋白比溶剂处理和阿司匹林治疗的SHR。用西洛他唑治疗，而不是阿司匹林，显著改善脑血流对L-N-5-（1-亚氨基乙基）鸟氨酸的反应。西洛他唑还增加了微循环的残余灌注，减少缺血后的脑损伤相比，车辆控制和aspiros. Conclusions，这些研究结果表明，西洛他唑，但不是阿司匹林，可以减轻缺血性脑损伤，通过维持内皮功能在SHR的大脑皮层。（中风。2011;42：2571-2577）。
Background and Purpose-It is well-established that hypertension leads to endothelial dysfunction in the cerebral artery. Recently, cilostazol has been used for the secondary prevention of ischemic stroke. Among antiplatelet drugs, phosphodiesterase inhibitors including cilostazol have been shown to have protective effects on endothelial cells. The aim of the present study is to investigate the effects of cilostazol and aspirin on endothelial nitric oxide synthase (eNOS) phosphorylation in the cerebral cortex, endothelial function, and infarct size after brain ischemia in spontaneously hypertensive rats (SHR).Methods-Five-week-old male SHR received a 5-week regimen of chow containing 0.1% aspirin, 0.1% cilostazol, 0.3% cilostazol, or the vehicle control. The levels of total and Ser(1177)-phosphorylated eNOS protein in the cerebral cortex were evaluated by Western blot. To assess the contribution of eNOS in maintaining cerebral blood flow, we monitored cerebral blood flow by laser-Doppler flowmetry after L-N-5-(1-iminoethyl)ornithine infusion. Additionally, we evaluated residual microperfusion using fluorescence-labeled serum protein and infarct size after transient focal brain ischemia.Results-In SHR, the blood pressure and heart rate were similar among the groups. Cilostazol-treated SHR had a significantly higher ratio of phospho-eNOS/total eNOS protein than vehicle-treated and aspirin-treated SHR. Treating with cilostazol, but not aspirin, significantly improved cerebral blood flow response to L-N-5-(1-iminoethyl)ornithine. Cilostazol also increased residual perfusion of the microcirculation and reduced brain damage after ischemia compared to vehicle control and aspirin.Conclusions-These findings indicate that cilostazol, but not aspirin, can attenuate ischemic brain injury by maintaining endothelial function in the cerebral cortex of SHR. (Stroke. 2011;42:2571-2577.)