Dumitrascu Rio, Koebrich Silke, Dony Eva, Weissmann Norbert, Savai Rajkumar, Pullamsetti Soni S, Ghofrani Hossein A, Samidurai Arun, Traupe Horst, Seeger Werner, Grimminger Friedrich, Schermuly Ralph T
University of Giessen Lung Center, Giessen, Germany.
BMC Pulm Med. 2008 Dec 17;8:25. doi: 10.1186/1471-2466-8-25.
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.
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建立小鼠肺动脉高压模型。
对接受不同剂量野百合碱吡咯静脉注射的动物进行生存研究、计算机断层扫描、组织学检查、支气管肺泡灌洗，并测量动脉血气和血流动力学。
野百合碱吡咯可诱导Sprague Dawley大鼠发生肺动脉高压。当注射到小鼠体内时，野百合碱吡咯在C57Bl6/N和BALB/c小鼠中诱导剂量依赖性死亡（剂量范围为6-15mg/kg体重）。在10mg/kg体重的剂量下，小鼠出现典型的早期急性肺损伤，其特征为肺水肿、中性粒细胞浸润、低氧血症和肺顺应性降低。在后期，注射野百合碱吡咯导致有限的肺纤维化，且无明显的肺动脉高压。
野百合碱和野百合碱吡咯的肺毒性在不同动物物种之间存在显著差异。
