Copple Bryan L, Banes Amy, Ganey Patricia E, Roth Robert A
Department of Pharmacology and Toxicology, B-346 Life Sciences Building, Michigan State University, East Lansing, Michigan 48824, USA.
Toxicol Sci. 2002 Feb;65(2):309-18. doi: 10.1093/toxsci/65.2.309.
Monocrotaline (MCT) is a pyrrolizidine alkaloid (PA) plant toxin that produces hepatotoxicity in people and animals. Human exposure to PAs occurs through consumption of contaminated grains and herbal remedies. Injection (ip) of MCT in rats produced dose-dependent hepatic parenchymal cell injury that was significant at 200 mg/kg. Injection of 300 mg/kg MCT produced time-dependent hepatotoxicity with significant injury beginning by 12 h after treatment. Histopathologic examination of liver sections revealed coagulative hepatocellular necrosis, widening of sinusoids and hemorrhage in centrilobular regions. MCT-induced damage to central venular endothelial cells (CVECs) and sinusoidal endothelial cells (SECs) in the liver was quantified using immunohistochemical staining and by increased plasma hyaluronic acid concentration. MCT damaged CVECs and SECs in the liver by 8 h after treatment. Extensive endothelial cell injury was restricted to centrilobular regions. To determine if damage to endothelial cells in the liver stimulated activation of the coagulation system, fibrin deposition was quantified using immunohistochemistry. Extensive fibrin deposition occurred in the liver after MCT treatment and was restricted to centrilobular regions. Interestingly, both endothelial cell damage and fibrin deposition preceded the onset of hepatic parenchymal cell injury. These results suggest that endothelial cell damage and fibrin deposition in centrilobular regions of the liver are prominent features of MCT-induced liver injury.
野百合碱（MCT）是一种吡咯里西啶生物碱（PA）植物毒素，可对人和动物产生肝毒性。人类通过食用受污染的谷物和草药接触PA。给大鼠腹腔注射MCT会产生剂量依赖性肝实质细胞损伤，在200mg/kg时损伤显著。注射300mg/kg MCT会产生时间依赖性肝毒性，治疗后12小时开始出现明显损伤。肝脏切片的组织病理学检查显示肝小叶中央区有凝固性肝细胞坏死、血窦增宽和出血。使用免疫组织化学染色并通过血浆透明质酸浓度升高来量化MCT对肝脏中央静脉内皮细胞（CVEC）和肝血窦内皮细胞（SEC）的损伤。治疗后8小时，MCT损伤了肝脏中的CVEC和SEC。广泛的内皮细胞损伤局限于肝小叶中央区。为了确定肝脏内皮细胞损伤是否刺激凝血系统激活，使用免疫组织化学对纤维蛋白沉积进行量化。MCT治疗后肝脏中出现广泛的纤维蛋白沉积，且局限于肝小叶中央区。有趣的是，内皮细胞损伤和纤维蛋白沉积均先于肝实质细胞损伤的发生。这些结果表明，肝脏小叶中央区的内皮细胞损伤和纤维蛋白沉积是MCT诱导肝损伤的突出特征。
