Schultze A E, Roth R A
Department of Pathology, Michigan State University, East Lansing 48824.
Toxicol Appl Pharmacol. 1993 Sep;122(1):7-15. doi: 10.1006/taap.1993.1166.
Administration to rats of monocrotaline pyrrole (MCTP), a putative metabolite of the pyrrolizidine alkaloid, monocrotaline, causes pulmonary microvascular thrombosis that is associated with vascular remodeling and pulmonary hypertension. It is possible that vascular thrombi contribute to the lesions that occur after MCTP treatment. Since MCTP is toxic to pulmonary endothelial cells and because the pulmonary endothelium is in a unique position to influence procoagulant and fibrinolytic reactions in the lungs, we examined changes in the procoagulant and fibrinolytic properties of cultured pulmonary artery endothelial cells exposed to MCTP to see if they might favor thrombosis. Monolayers of confluent bovine pulmonary arterial endothelial cells received a single administration of MCTP or N,N-dimethylformamide vehicle, and the media or lysates were examined at 4, 24, 48, or 120 hr after treatment. MCTP caused a time-dependent cell detachment and an increase in release of lactate dehydrogenase into culture medium. Although cell numbers decreased dramatically with time, the protein concentration of cell monolayer lysates was unchanged by treatment. MCTP treatment caused no change in the amount of tissue factor activity/micrograms cellular protein in bovine endothelial cell lysates and only a small increase in the activity of Factor V in the culture medium at 120 hr. In addition, the medium from bovine endothelial cells treated with MCTP had a time-dependent increase in the activity of plasminogen activators and a decrease in the activity of plasminogen activator inhibitors. Thus bovine endothelial cells exposed to MCTP in vitro do not produce changes in these procoagulant or fibrinolytic properties that would explain the thrombosis observed in vivo.
给大鼠注射吡咯里西啶生物碱野百合碱的一种假定代谢产物——野百合碱吡咯（MCTP），会导致肺微血管血栓形成，这与血管重塑和肺动脉高压有关。血管血栓可能是MCTP治疗后出现病变的原因。由于MCTP对肺内皮细胞有毒性，且肺内皮细胞在影响肺内促凝血和纤溶反应方面处于独特位置，我们研究了暴露于MCTP的培养肺动脉内皮细胞的促凝血和纤溶特性变化，以确定它们是否可能促进血栓形成。汇合的牛肺动脉内皮细胞单层接受单次MCTP或N，N - 二甲基甲酰胺载体给药，并在处理后4、24、48或120小时检查培养基或裂解物。MCTP导致细胞随时间依赖性脱落，并使乳酸脱氢酶释放到培养基中的量增加。尽管细胞数量随时间急剧减少，但处理后细胞单层裂解物的蛋白质浓度未发生变化。MCTP处理对牛内皮细胞裂解物中组织因子活性/微克细胞蛋白的量没有影响，仅在120小时时培养基中因子V的活性略有增加。此外，用MCTP处理的牛内皮细胞培养基中纤溶酶原激活剂的活性随时间增加，而纤溶酶原激活剂抑制剂的活性降低。因此，体外暴露于MCTP的牛内皮细胞在这些促凝血或纤溶特性方面没有产生变化，无法解释体内观察到的血栓形成。
