摘要
目的:探讨4种肺动脉高压(PH)动物模型肺血管重构模式的差异。方法:雄性SD大鼠(350-400g),分别通过腹主动脉-腔静脉分流(A-VF,n=10)、左肺切除(PE,n=10)、野百合碱注射(MCT,n=10)、左肺切除+MCT(PE+MCT,n=12)4种方法建立PH模型。检测平均肺动脉压力(mPAP)、RV/(LV+S)重量比值、肺小动脉中膜厚度百分比(WT%)、无肌性动脉肌化程度和新生内膜(neointima)形成、新生内膜增殖度和血管阻塞计分(VOS)。结果:在PE+MCT组(肺切除术后5周,MCT注射后4周)右肺腺泡内血管出现了新生内膜病变,其它组均没有新生内膜病变形成。PE+MCT组的动物出现了严重的右心室肥大,动脉中膜明显增厚,平均肺动脉压(mPAP)和无肌性血管肌化程度显著增加;A-VF、PE和MCT组仅形成轻-中度的右心室肥大、mPAP升高和小动脉肌化。结论:左肺切除联合应用MCT能成功诱导大鼠PH新生内膜模型,该模型能更好地模拟人类严重PH的病理改变,是研究梗阻性PH更为适用的动物模型。
AIM ： To explore the differentiation of the pattern of pulmonary vascular remodeling in response to injury by comparing 4 approaches in established pulmonary hypertension model in rat. METHODS ： 52 male Sprague - Dawley rats （350 -400g） were randomized into： abdominal aortocaval fistula shunting group （A -VF, n = 10 ） ; left lung pneumonectomy group （ PE, n = 10） ; monocrotaline injection （ subcutaneous 60 mg,/kg） group （ MCT, n = 10） and MCT injection 7 days after left lung resection group（ PE ＋ MCT, n = 12）. Ten additional rats were served as control. Hemody- namic measurements and morphological parameters relevant to pulmonary vascular remodeling pattern were performed in each group of rats. RESULTS ： Neointima proliferation was observed in 88.5% of right lung intra - acinar arteries 5 weeks after pneumonectomy in PE ＋ MCT rats,and vascular occlusion score （VOS） was 1.71 ±0. 13 in those animals, while such lesions did not develop in other groups. Animals with neointimal pattern of remodeling developed significant right ventricular hypertrophy and mean pulmonary arterial pressure elevation was more severe than that in the rest experimental groups, medial hypertrophy of small pulmonary arteries and distal arteriole muscularization developed in PE ＋ MCT rats were also more significant than those in other groups of rats. CONCLUSION ： The neointimal model of pulmonary hypertension can be successfully established by introduction of hemodynamic stress to the injury of MCT injection rats and should be utilized as a preferable model for the research on human severe obstructive pulmonary hypertension.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第2期289-293,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.30560159)
关键词
肺动脉高压
血管重建
新生内膜
Pulmonary arterial hypertension
Vascular remodeling
Neointima
