Urizar R E, Sherer G, Tartaglia A, Pickering R J, Dodds W J
Lab Invest. 1975 Mar;32(3):270-8.
Under the proper experimental conditions, disseminated intravascular coagulation,"an intermediary mechanism of disease," results in the classic endotoxin-induced generalized Shwartzman reaction. Other substances, such as liquoid, a highly negatively charged anticoagulant, trigger a generalized Shwartzman reaction-like phenomenon in rabbits. We studied the effects of a single high intravenous dose of liquoid (12.5 mg.) upon the rat's coagulation and complement systems and their correlation with the kidney morphology by light, fluorescence, and electron microscopy. Thrombin time was prolonged; fibrinogen, plasminogen, and factors VIII and XII concentrations were markedly decreased, whereas fibrin degradation products were increased in the experimental animals when compared with the saline-injected controls (p greater than 0.001). Total hemolytic complement, hemolytic activity of terminal components (C3 to C9), and C3 protein concentration were significantly reduced (p greater than 0.001). The liquoid-injected rats developed cortical necrosis and manifested oliguria and anuria, with elevated blood urea nitrogen levels, when survival was longer than 3 hours. Histologically, thrombi of fibrin-like material filled the glomerular capillaries. Deposits of fibrin, and also of immunoglobulin G and C3, were readily identifiable by specific immunofluorescence, Linear or granular fluorescent deposits (or both) along the glomerular basement membranes and in the mesangium were observed. Electron microscopy demonstrated necrosis of glomeruli and abundant thrombi of fluffy, compact granular, or fibrillar electron-dense material. No typical fibrin periodicity was detected. These experiments support the concept of activation of the coagulation and the complement systems. We postulate that liquoid produced not only a consumptive coagulopathy in the rat but also a direct or perhaps anindirect activation of complement. Whether this latter has occurred through the classic or an alternate pathway remains to be elucidated.
在适当的实验条件下，弥散性血管内凝血这一“疾病的中间机制”会导致典型的内毒素诱导的全身性施瓦茨曼反应。其他物质，如液态抗凝剂（一种带高度负电荷的抗凝剂），可在兔子身上引发类似全身性施瓦茨曼反应的现象。我们研究了静脉内单次高剂量注射液态抗凝剂（12.5毫克）对大鼠凝血和补体系统的影响，以及通过光学显微镜、荧光显微镜和电子显微镜观察到的这些影响与肾脏形态的相关性。与注射生理盐水的对照组相比，实验动物的凝血酶时间延长；纤维蛋白原、纤溶酶原以及因子VIII和XII的浓度显著降低，而纤维蛋白降解产物增加（p>0.001）。总溶血补体、末端成分（C3至C9）的溶血活性以及C3蛋白浓度均显著降低（p>0.001）。注射液态抗凝剂的大鼠出现皮质坏死，并表现为少尿和无尿，存活时间超过3小时时血尿素氮水平升高。组织学检查显示，纤维蛋白样物质的血栓填充了肾小球毛细血管。通过特异性免疫荧光很容易识别出纤维蛋白以及免疫球蛋白G和C3的沉积物。观察到沿肾小球基底膜和系膜有线性或颗粒状荧光沉积物（或两者皆有）。电子显微镜显示肾小球坏死，并有大量蓬松、紧密颗粒状或纤维状电子致密物质的血栓。未检测到典型的纤维蛋白周期性。这些实验支持了凝血和补体系统激活的概念。我们推测，液态抗凝剂不仅在大鼠中导致了消耗性凝血病，还直接或可能间接激活了补体。后者是通过经典途径还是替代途径发生的，仍有待阐明。
