Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury.
Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury.
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DOI：
10.1186/1471-2466-8-25
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发表时间：
2008-12-17
影响因子：
3.1
通讯作者：
Schermuly RT
中科院分区：
文献类型：
--
作者：
Dumitrascu R;Koebrich S;Dony E;Weissmann N;Savai R;Pullamsetti SS;Ghofrani HA;Samidurai A;Traupe H;Seeger W;Grimminger F;Schermuly RT
需要新的小鼠慢性肺动脉高压动物模型。注射野百合碱是大鼠肺动脉高压的既定模型。本研究的目的是通过注射活性代谢物野百合碱吡咯来建立肺动脉高压的小鼠模型。对静脉注射不同剂量野百合碱吡咯的动物进行生存研究、计算机断层扫描、组织学、支气管肺泡灌洗，并测量动脉血气和血流动力学。野百合碱吡咯诱导斯普拉格道利大鼠肺动脉高压。当注射到小鼠体内时，野百合碱吡咯会引起 C57Bl6/N 和 BALB/c 小鼠的剂量依赖性死亡率（剂量范围为 6-15 毫克/千克体重）。在10毫克/公斤体重的剂量下，小鼠出现典型的早期急性肺损伤，其特征是肺水肿、中性粒细胞流入、低氧血症和肺顺应性降低。后期注射野百合碱吡咯导致肺纤维化有限，无明显肺动脉高压。野百合碱和野百合碱吡咯的肺毒性在动物物种之间有很大差异。
New animal models of chronic pulmonary hypertension in mice are needed. The injection of monocrotaline is an established model of pulmonary hypertension in rats. The aim of this study was to establish a murine model of pulmonary hypertension by injection of the active metabolite, monocrotaline pyrrole. Survival studies, computed tomographic scanning, histology, bronchoalveolar lavage were performed, and arterial blood gases and hemodynamics were measured in animals which received an intravenous injection of different doses of monocrotaline pyrrole. Monocrotaline pyrrole induced pulmonary hypertension in Sprague Dawley rats. When injected into mice, monocrotaline pyrrole induced dose-dependant mortality in C57Bl6/N and BALB/c mice (dose range 6–15 mg/kg bodyweight). At a dose of 10 mg/kg bodyweight, mice developed a typical early-phase acute lung injury, characterized by lung edema, neutrophil influx, hypoxemia and reduced lung compliance. In the late phase, monocrotaline pyrrole injection resulted in limited lung fibrosis and no obvious pulmonary hypertension. Monocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.