Novelli G P, Casali R, Bonizzoli M, Giorgi L, Lemma M, Piscitelli P
Istituto di Anestesiologia e Rianimazione, Università degli Studi-Firenze.
Minerva Anestesiol. 1995 Dec;61(12):509-13.
Circulatory shock, especially endotoxin shock, is characterized by the release of a large number of mediators, among which proteases play a key role. The production of oxygen free radicals into the extracellular space and the increase of capillary permeability is one of the most important consequences of that phenomenon. In order to evaluate the efficacy of gabexate mesilate (Foy) in preventing such increase of microvascular permeability, an experimental model of endotoxin shock was used.
Experiments were performed on the mesocecum of male Wistars rats, fluorescent labeled bovine albumine was injected intrarterially to evaluate the capillary permeability and the mesocecum microcirculation was observed by fluorescent light. The control group received saline i.v.; the II group received a DL 100 of E. coli endotoxin (DIFCO 0111: B4); the III and the IV group received a continuous infusion or topical application of gabexate mesilate respectively, before the administration of endotoxin. To evaluate capillary permeability and to quantify the degree of extravasion by counting the number of leaky sites, fluorescent labelled bovine albumin was injected i.v. and mesocecum was observed with fluorescent microscopy for 2 hours.
Capillary permeability did not increase in control rats; it largely increased in rats receiving endotoxin i.v. but it did not almost increased in rats receiving gabexate mesilate (Foy) that prevents the increase of capillary permeability that was observed in the group treated with endotoxin alone.
循环性休克,尤其是内毒素休克,其特征是大量介质的释放,其中蛋白酶起关键作用。氧自由基释放到细胞外空间以及毛细血管通透性增加是该现象最重要的后果之一。为了评估甲磺酸加贝酯(福怡)预防微血管通透性增加的效果,采用了内毒素休克实验模型。
实验在雄性Wistar大鼠的盲肠系膜上进行,动脉内注射荧光标记的牛白蛋白以评估毛细血管通透性,并用荧光观察盲肠系膜微循环。对照组静脉注射生理盐水;第二组静脉注射100DL的大肠杆菌内毒素(DIFCO 0111:B4);第三组和第四组在内毒素给药前分别持续输注或局部应用甲磺酸加贝酯。为了评估毛细血管通透性并通过计数渗漏部位的数量来量化外渗程度,静脉注射荧光标记的牛白蛋白,并用荧光显微镜观察盲肠系膜2小时。
对照组大鼠的毛细血管通透性未增加;静脉注射内毒素的大鼠毛细血管通透性大幅增加,但接受甲磺酸加贝酯(福怡)的大鼠毛细血管通透性几乎未增加,甲磺酸加贝酯可预防单独用内毒素治疗的组中观察到的毛细血管通透性增加。