急性缺氧型肺动脉高压动物模型制备

Preparation and identification of animal model with hypoxia-induced pulmonary artery hypertension

目的制备兔急性缺氧型PAH模型,探讨PAH对左心室功能及其心肌重塑与细胞凋亡影响。方法将实验兔30只分为缺氧PAH组(20只)和对照组(10只),通过测定血流动力学、血液流变学、体重量(BW)与左心室重量(LVW)比值、心室病理组织学观察和超微结构观察等指标了解PAH对左心室影响。结果缺氧-PAH组PaO2明显低于对照组,pH,PaCO,HCO-与对照组比较无统计学差异;mPAP,mRVP显著升高(P<0.001);右心室肥大指数增大;红细胞压积、红细胞刚性指数及其聚集指数明显增大(P<0.05);血浆粘度无改变。镜下观察,缺氧-PAH组其肺动脉肌层稍有增厚,管腔轻度狭窄,右心室心肌细胞胞体增大,胞浆肿胀,空泡变性,胞核增大;左心室基本指标检测结果缺氧-PAH组其LVW/BW增加,而LVSP,MAP和+dp/dt max无显著性改变(P>0.05),左室壁病变均显著重于对照组(P<0.01)。电镜下,缺氧-PAH组动物心肌细胞表现为线粒体高度肿胀,嵴溶解消失形成打泡,肌浆网高度扩张,肌原纤维排列紊乱,Z线增粗,核染色质凝结及边聚,细胞内及间质重度水肿。结论通过低氧通气方法可成功制备PAH动物模型,PAH对左心室功能及其心肌重塑与细胞凋亡存在影响。

Objective To preparer hypoxia-induced pulmonary artery hypertension rabbit model and investigate the affection of pulmonary artery hypertension（PAH） on the left ventricular myocardial remodel and dysfunction. Methods Thirty experimental rabbits were divided into the control group （n = 10） and the hypoxia-induced PAH group （n = 20）randomly. The preparation effective of hypoxia- induced pulmonary artery hypertension rabbit moel was identificated by analyzing the data of blood gas analysis, haemodynamics, RVHI and histopathology observation in cardiac ventricle and cardiac ventricle. The data of haemodynamics, hemorheology, the ratio of body weight and left ventricle weight and histopathology and ultramicrostructure observation in cardiac ventricle were analyzed to investigate the affection of pulmonary artery hypertension（PAH） on the left ventricular myocardial remodel and dysfunction. ResultsPaO2 in PAH group was lower than the control group significantly. However, the difference between PAH group and control group in pH, PaCO and HCO^- was insignificant. RVHI of PAH group was higher than the control group. Contrast with the control group, pulmonary artery in PAH group was observed with thicker muscular layer and narrow lumens under light microscopy. Myocardium cell of right ventricle in PAH group was observed with large cell body, swelling endochylema, vacuolar degeneration and enlarge nucleus. Basic index of the left ventricular in hypoxia-induced pulmonary artery hypertension group： Contrast with the control group, LVW/BW in PAH group increased significantly. But the increasing of LVSP,MAP and ＋dp/ dt max were insignificant（P〉0.05）. In PAH group, the values of dp/dtmax reduced obviously with prolong T value and higher LVEDP （P〈0.01）. The chondriosomes swelling,sarcoplas micreticula dilatation, myofibrillae solution and edema of inside and outside of the celles, accumulation of Z-line material or hyperplasia of the mitochondria were observed under electron microscopy in PAH group. Conclusion Hypoxia-induced pulmonary artery hypertension animal model can be produced by hypoxia machine ventilation. PAH may play key role in the left ventricular myocardial remodel, dysfunction and left ventricular myocardial cell apoptosis.