稳定的前列环素类似物伊洛前列素对仓鼠颊袋微血管张力和通透性的作用

B. Müller, M. Schmidtke, W. Witt
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引用次数: 54

摘要

为了进一步阐明前列环素和伊洛前列素治疗周围性缺血性疾病的作用机制,我们在麻醉的叙利亚仓鼠颊袋中使用活体视频显微镜研究了炎症介质和缺血诱导的微血管张力、毛细血管密度和静脉通透性增加的作用,并定量研究了荧光素标记葡聚糖(FITC-D)的静脉渗漏;70000 Mw)。非降压、血小板聚集抑制剂量0.5 μg/kg/min静脉滴注伊洛前列素可显著增加小动脉、小静脉直径和灌注毛细血管密度,拮抗白三烯D4 (LTD4)诱导的血管收缩,降低灌注毛细血管密度;Iloprost可显著抑制组胺(10−5 M)、血清素(10−5 M)、缓激肽(10−6 M)和缺血30min后再灌注引起的FITC-D静脉渗漏。局部应用伊洛前列素(10−8 M),动脉内灌注前列腺素E1 (PGE1);2.0 μg/kg/min)和外用福斯柯林(10 ~ 5 M)也能减轻组胺引起的静脉FITC-D渗漏,而外用PGE1 (10 ~ 7M)和静脉滴注硝苯地平(30 μg/kg + 10 μg/kg/min)均无效果。由此可见,伊洛前列素通过改善组织灌注、拮抗介质诱导的组织水肿和血管痉挛等微血管作用,有助于提高缺血性疾病的治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Action of the stable prostacyclin analogue iloprost on microvascular tone and -permeability in the hamster cheek pouch

In order to further elucidate the mechanisms involved in therapeutic effects of prostacyclin and Iloprost in peripheral ischemic disease, the actions on microvascular tone, capillary density, and increases in venular permeability induced by inflammatory mediators and by ischemia were investigated in the cheek pouch of anaesthetized Syrian hamsters using intravital videomicroscopy and - for quantification of vascular permeability - venular leakage of fluorescein-labelled dextran (FITC-D; Mw 70,000). Iloprost at the nonhypotensive, platelet aggregation-inhibiting dose of 0.5 μg/kg/min i.v. significantly increased the diameters of arterioles and venules and the density of perfused capillaries and antagonized vasoconstriction and decrease of perfused capillary density as induced by Leukotriene D4 (LTD4; 10−7 M). Iloprost significantly antagonized venular leakage of FITC-D induced by histamine (10−5 M), serotonin (10−5 M), bradykinin (10−6 M) and reperfusion after 30 min ischemia. Topical application of Iloprost (10−8 M), intraarterial infusion of Prostaglandin E1 (PGE1; 2.0 μg/kg/min), and topical Forskolin (10−5 M) also attenuated histamine-induced venular FITC-D leakage, while topical PGE1 (10−7M) and i.v. infusion of Nifedipine (30 μg/kg + 10 μg/kg/min) were not effective.

It is concluded, that microvascular effects of Iloprost by improvement of tissue perfusion and functional antagonism of mediator-induced tissue edema and vasospasm could contribute to therapeutic effectiveness in ischemic diseases.

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