Sakurai N, Sugimoto K, Sugihara H, Shirasawa H, Muro H, Kaneko M, Nikai T, Shibata K
Am J Pathol. 1986 Feb;122(2):240-51.
Glomerular injury was produced in mice after a single LD50 intravenous dose of purified 100-pace snake venom (Agkistrodon acutus). Characteristic features in glomeruli where the venom was demonstrated immunohistochemically included cystic lesions of the capillary tufts, thrombosis, subsequent proliferative and sclerotic changes, and crescent formation. Venom was recognized immunohistochemically in the glomerular endothelium, visceral basement membrane, mesangium, epithelium, and Bowman's capsule. Venom transfer across the basement membrane or into cells required less than 2 hours. Within this period mesangiolysis occurred due to the protease activity of the venom. Cystic lesions with fibrin thrombi then developed, which were replaced by proliferative and sclerotic changes after 3 days. Crescent formation began within 48 hours and was completed within a few days. Microangiography revealed hemodynamic changes in the intrarenal vasculature after venom treatment. Immune complex deposition was not found in any tissue. The study demonstrates the moderately constant potency (LD50) of Agkistron acutus venom, and documents it as a useful tool for quantitative studies of renal lesions.
单次静脉注射半数致死量(LD50)的纯化百步蛇毒(尖吻蝮)后,小鼠出现肾小球损伤。免疫组化显示有毒素的肾小球的特征性表现包括毛细血管袢的囊性病变、血栓形成、随后的增殖性和硬化性改变以及新月体形成。免疫组化在肾小球内皮、脏层基底膜、系膜、上皮和鲍曼囊中识别出毒素。毒素穿过基底膜或进入细胞所需时间少于2小时。在此期间,由于毒素的蛋白酶活性发生了系膜溶解。随后出现伴有纤维蛋白血栓的囊性病变,3天后被增殖性和硬化性改变所取代。新月体形成在48小时内开始,并在几天内完成。微血管造影显示毒素处理后肾内血管系统的血流动力学变化。在任何组织中均未发现免疫复合物沉积。该研究证明了尖吻蝮蛇毒的半数致死量(LD50)具有一定的稳定性,并将其作为肾损伤定量研究的有用工具记录下来。