Hilliker K S, Garcia C M, Roth R A
Res Commun Chem Pathol Pharmacol. 1983 May;40(2):179-97.
Treatment of rats with monocrotaline (MCT) or its reactive pyrrole metabolite, dehydromonocrotaline (MCTP), injures pulmonary capillary endothelium and other lung cell types. The mechanism by which pulmonary damage occurs is unknown. To investigate the possibility that the metabolites of MCT can injure lung cells directly, slices of lung from male Sprague-Dawley rats were incubated with chemically synthesized MCTP (0.1-1.0 mM). The ability of the slices to accumulate 5-hydroxytryptamine (5HT) was then examined. After 5 hours exposure to MCTP in vitro, there was no change in either 5HT or PQ uptake at any of the MCTP concentrations tested. Similar results were obtained when lung slices were incubated with liver slices and MCT to generate MCT metabolites in vitro. In contrast, treatment in vivo with MCTP resulted in a 35% decrease in the uptake of 5HT and a 15% decrease in the uptake of PQ by lung slices 14 days after treatment. These results suggest that damage does not occur by direct interaction of MCTP with the lung tissue or that functional injury is slow to develop. Alternatively, the damage in vivo may be mediated by factors not present in the sliced tissue.
用野百合碱（MCT）或其活性吡咯代谢物脱氢野百合碱（MCTP）处理大鼠会损伤肺毛细血管内皮细胞和其他肺细胞类型。肺损伤发生的机制尚不清楚。为了研究MCT的代谢产物是否能直接损伤肺细胞，将雄性Sprague-Dawley大鼠的肺切片与化学合成的MCTP（0.1 - 1.0 mM）一起孵育。然后检测切片积累5-羟色胺（5HT）的能力。在体外暴露于MCTP 5小时后，在所测试的任何MCTP浓度下，5HT或PQ摄取均无变化。当肺切片与肝切片以及MCT一起在体外孵育以生成MCT代谢产物时，也获得了类似的结果。相比之下，在体内用MCTP处理后14天，肺切片对5HT的摄取减少了35%，对PQ的摄取减少了15%。这些结果表明，损伤不是由MCTP与肺组织的直接相互作用引起的，或者功能损伤发展缓慢。或者，体内损伤可能由切片组织中不存在的因素介导。
