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首页> 外文期刊>Journal of vascular research >Development and characterization of an animal model of severe pulmonary arterial hypertension.
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Development and characterization of an animal model of severe pulmonary arterial hypertension.

机译：严重肺动脉高压动物模型的开发和表征。

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摘要

Pulmonary arterial hypertension (PAH) is a serious pathological phenomenon with poor prognosis, which is associated with morphological as well as hemodynamic alteration of the pulmonary circulation. To establish an animal model mimicking severe human PAH, we combined 2 well-described procedures, i.e. exposure to hypobaric chronic hypoxia and administration of monocrotaline hydrochloride in rats. Compared to a single procedure, the combined procedure induced more severe right ventricle hypertrophy and an increase in right ventricle systolic pressure. Histological examination on the combined procedure model revealed a severe medial hypertrophy as well as occlusive vascular changes of the intra-acinar pulmonary arteries with endothelial lesions. It is noteworthy that severe alterations including concentric neointimal thickening, abnormal endothelial proliferation, plexiform lesions and vascular occlusion with fibrin thrombi were observed in the combined pulmonary hypertension model when exposed to a long period of hypoxia. The present data indicate that a combined treatment of monocrotaline injection and hypobaric chronic hypoxia exposure produces more severe hemodynamic changes and histological alterations. Since human PAH diagnosed in clinical practice is often severe, this combined treatment animal model could be useful to identify relevant therapeutic targets acting on both hemodynamic and structural alterations of the pulmonary circulation.
机译：肺动脉高压（PAH）是一种严重的病理现象，预后较差，与肺循环的形态学和血液动力学改变有关。为了建立模拟重度人PAH的动物模型，我们结合了2种详细描述的程序，即暴露于低压慢性缺氧和大鼠单药盐酸克crocroline的给药。与单一手术相比，合并手术引起更严重的右心室肥大和右心室收缩压升高。联合手术模型的组织学检查显示，严重的内侧肥大以及具有内皮病变的髋臼内肺动脉闭塞性血管改变。值得注意的是，在长期缺氧的合并肺动脉高压模型中，观察到严重的改变，包括同心的新内膜增厚，内皮异常增生，丛状病变和纤维蛋白栓塞的血管闭塞。目前的数据表明，单芥子碱注射液和低压慢性低氧暴露的联合治疗会产生更严重的血液动力学变化和组织学改变。由于在临床实践中诊断出的人PAH通常很严重，因此这种联合治疗的动物模型可用于识别对肺循环的血液动力学和结构改变均起作用的相关治疗靶标。

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