Gumprecht L A, Beasley V R, Weigel R M, Parker H M, Tumbleson M E, Bacon C W, Meredith F I, Haschek W M
Department of Veterinary Pathobiology, University of Illinois, Urbana 61802, USA.
Toxicol Pathol. 1998 Nov-Dec;26(6):777-88. doi: 10.1177/019262339802600610.
The fumonisin (FB) mycotoxins induce liver injury in all species but induce fatal pulmonary edema (PE) only in pigs. They inhibit ceramide synthase in the sphingolipid biosynthetic pathway. To study the pathogenesis of PE, we examined the early events in the development of FB-induced PE and hepatotoxicity in pigs. Pigs were fed FB-contaminated culture material at 20 mg fumonsin B1 (FB1)/kg body weight/day. Groups of 4 pigs were to be euthanatized on 0, 1, 2, 3, 4, or 5 days after initial exposure to FB or when PE developed. Pigs developed PE beginning on day 3; none survived beyond day 4. Progressive elevations in hepatic parameters, including serum enzymes, bile acids, total bilirubin, and histologic changes, began on day 2. Early histologic changes in the lung (day 2) consisted of perivascular edema followed by interlobular and peribronchial edema. Ultrastructurally, alveolar endothelial cells contained unique accumulations of membranous material in the cytocavitary network beginning on day 2. Marked elevations in sphinganine, sphingosine, and their ratio began on day 1 for all tissues whether affected morphologically (lung, liver) or not (kidney, pancreas). The membranous material in endothelial cells may be accumulations of sphingoid bases with damage to the cytocavitary network. Thus, FB induces early elevations in sphingolipids and hepatic injury, followed by alveolar endothelial damage, which may be the critical event in the pathogenesis of PE in pigs.
伏马菌素（FB）类霉菌毒素可在所有物种中诱发肝损伤，但仅在猪中诱发致命性肺水肿（PE）。它们抑制鞘脂生物合成途径中的神经酰胺合酶。为了研究PE的发病机制，我们检测了FB诱发猪PE和肝毒性过程中的早期事件。给猪喂食受FB污染的培养物，剂量为20毫克伏马菌素B1（FB1）/千克体重/天。每组4头猪，在初次接触FB后0、1、2、3、4或5天，或在PE出现时实施安乐死。猪在第3天开始出现PE；第4天后无一存活。从第2天开始，包括血清酶、胆汁酸、总胆红素在内的肝脏参数逐渐升高，同时出现组织学变化。肺的早期组织学变化（第2天）包括血管周围水肿，随后是小叶间和支气管周围水肿。超微结构上，从第2天开始，肺泡内皮细胞的细胞腔网络中出现独特的膜性物质积聚。无论形态学上是否受影响（肺、肝），所有组织（肾、胰腺）中的鞘氨醇、鞘氨醇及其比值在第1天开始显著升高。内皮细胞中的膜性物质可能是鞘脂碱基的积聚，并伴有细胞腔网络的损伤。因此，FB诱导鞘脂早期升高和肝损伤，随后是肺泡内皮损伤，这可能是猪PE发病机制中的关键事件。
