Thompson K G, Jones D H, Sutherland R J, Camp B J, Bowers D E
J Comp Pathol. 1983 Apr;93(2):319-29. doi: 10.1016/0021-9975(83)90018-x.
The earliest lesion in rabbits dosed orally with 2 mg of sporidesmin per kg of body weight was necrosis of occasional hepatocytes 1 day after dosing. The most consistent lesion was a severe necrotizing cholangitis of medium and large-sized intrahepatic and extrahepatic bile ducts, first seen 2 days after dosing. Similar lesions were also present in the gall bladder of some rabbits. Expansion of portal triads with fibrous tissue and proliferating bile ductules progressed to pseudo-lobulation by 21 days. Other hepatic changes observed irregularly included large infarcts at the periphery of some lobes, and multiple small foci of coagulation necrosis in midzonal and periportal regions. Vascular necrosis and thrombosis, invariably adjacent to necrotic bile ducts, was presumably responsible for the hepatic necrosis. Serum cholesterol and total bilirubin concentrations and GGT activity reached peaks 15 days after dosing and were useful indicators of the severity of biliary lesions. Serum ID activity was the most useful indicator of hepatic necrosis following oral dosing with sporidesmin. The similarity between hepatobiliary lesions observed in sheep and rabbits with experimental sporidesmin toxicity suggests that the rabbit would be a useful model for studying methods of treatment and prevention of "facial eczema" in ruminants.
给体重每千克口服2毫克孢子菌素的兔子，最早的病变是给药1天后偶尔出现肝细胞坏死。最常见的病变是肝内和肝外中、大型胆管的严重坏死性胆管炎，给药2天后首次出现。一些兔子的胆囊也有类似病变。到21天时，门管区纤维组织增生和胆管小分支增生发展为假小叶。其他偶尔观察到的肝脏变化包括一些肝叶周边的大梗死灶，以及中区和门周区域的多个小凝固性坏死灶。血管坏死和血栓形成总是与坏死胆管相邻，可能是肝脏坏死的原因。血清胆固醇、总胆红素浓度和γ-谷氨酰转移酶活性在给药15天后达到峰值，是胆管病变严重程度的有用指标。血清吲哚胺2,3-双加氧酶（ID）活性是口服孢子菌素后肝脏坏死最有用的指标。在绵羊和兔子中观察到的实验性孢子菌素毒性引起的肝胆病变相似，这表明兔子将是研究反刍动物“面部湿疹”治疗和预防方法的有用模型。
