左肺切除联合颈静脉注射脱氢野百合碱构建肺动脉高压小鼠模型的肺血管重构特点

  目的  比较左肺切除、颈静脉注射脱氢野百合碱、左肺切除联合颈静脉注射脱氢野百合碱三种方法构建肺动脉高压（PAH）小鼠模型的差异和肺血管重构的特点，寻找与临床发病机制接近的PAH动物模型，为深入研究重度PAH的发病机制提供良好的模型基础。  方法  取59只C57BL/6雄性小鼠（10～12周，24～30 g），随机分为对照组（n=9）、左肺切除组（PE组，n=15）、颈静脉注射脱氢野百合碱组（MCTP组，n=15）和左肺切除联合颈静脉注射脱氢野百合碱组（P+M组，n=20），通过检测右心室收缩压（RVSP）、右心室肥厚指数（RV/LV+S）、肺动脉中膜厚度百分比（WT%）、非肌性肺动脉肌化程度、新生内膜形成情况和血管阻塞评分（VOS）评价造模效果及肺血管重构的特点。  结果  ①与对照组比较，P+M组的RVSP、RV/LV+S、WT%、小肺动脉肌化程度均增加（P<0.01）；MCTP组表现为轻度的RVSP升高、右心室肥厚、中膜增厚和小肺动脉肌化程度增加（P<0.05）；PE组上述指标并无明显改变（P>0.05）。②P+M组腺泡内肺动脉可观察到新生内膜形成导致管腔明显狭窄，VOS为（1.25±0.80）分（P<0.001），MCTP组和PE组均未观察到新生内膜形成，VOS为0分（P>0.05）。  结论  左肺切除联合颈静脉注射脱氢野百合碱可诱导小鼠形成重度PAH，该模型能较好模拟临床重度PAH的特征性病理改变，即新生内膜形成。

Pulmonary Vascular Remodeling Characteristics of Pulmonary Arterial Hypertension Mouse Model Induced by Left Pneumonectomy and Jugular Vein Injection of Monocrotaline Pyrrole

  Objective  To compare and investigate the differences and characteristics of pulmonary vascular remodeling in three mouse models of pulmonary arterial hypertension (PAH) constructed by left pneumonectomy, jugular vein injection of monocrotaline pyrrole, and left pneumonectomy combined with jugular vein injection of monocrotaline pyrrole, to explore for a PAH animal model that approximates the clinical pathogenesis of PAH, and to create a model that will provide sound basis for thorough investigation into the pathogenesis of severe PAH.  Methods  59 male C57/BL mice (10-12 weeks, 24-30 g) were randomized into four groups, a control group (n=9), a group that had left pneumonectomy (PE, n=15), a group that had jugular vein injection of monocrotaline pyrrole (MCTP, n=15), and the last group that had left pneumonectomy combined with jugular injection of monocrotaline pyrrole (P+M, n=20). To evaluate the effect of modeling and the characteristics of pulmonary vascular remodeling, hemodynamic and morphological parameters, including right ventricular systolic pressure (RVSP), right ventricle/(left ventricle plus septum) (RV/LV+S), percent of wall thickness in the pulmonary artery (WT%), muscularization of non-muscular arteries, neointima formation, and vascular obstruction score (VOS), were measured in each group.   Results  1) Compared with those of the control group, the RVSP, RV/LV+S, WT%, and the degree of small pulmonary arteries muscularization in the P+M group were significantly increased (P<0.01). The MCTP group had just slightly higher findings for these indicators (P<0.05), while no significant change in these indicators was observed in the PE group (P>0.05). 2) Neointima formation in the acinus pulmonary arteries, which caused obvious stenosis of the lumen, was observed in the P+M group, the VOS being 1.25±0.80 points (P<0.001). In contrast, neointima formation was not observed in the MCTP group or the PE groups, the VOS being 0 point (P>0.05).  Conclusion  Left pneumonectomy combined with jugular intravenous injection of MCTP could induce severe PAH formation in mouse. The model provides a good simulation of neointima formation, the characteristic pathological change of clinical severe PAH.