摘要
目的:建立一种新的低压低氧性肺动脉高压大鼠模型,为临床治疗肺动脉高压提供新药筛选方法。方法:选用成年Wistar雄性大鼠,随机分为对照组和低压低氧组。对照组动物在正常环境中饲养,低压低氧组动物在低压低氧舱(大气压约50kPa,氧浓度10%)中饲养,连续4周。分别于1周、2周、4周分批给低压低氧组大鼠腹腔内注射戊巴比妥钠40mg/kg进行麻醉。测定大鼠肺血流动力学指标、右室肥厚指标(质量指数),检测肺血管病理和观察肺小动脉内皮细胞、平滑肌细胞的超微结构改变。结果:①低压低氧组大鼠平均肺动脉压和右室压力均明显高于对照组(P<0.01),并随低氧时间的延长而呈逐渐增高的趋势,但不同低氧时间的比较差异无统计学意义。低压低氧组大鼠平均颈总动脉压和心率与对照组相比差异无统计学意义。②右室重量测定结果表明低氧1周时,尚未出现明显的右室肥厚表现;低氧2周后,右室肥厚指标明显升高,与对照组和低氧1周时相比差异有统计学意义(P<0.01);低氧4周后,上述指标更较2周时显著增高(P<0.01)。③低压低氧组血管壁中层厚度占外径的百分比、血管壁中层横截面积占血管总横截面积的百分比均显著高于对照组(P<0.01),并随低氧时间的延长而逐渐增高,不同低氧时间的比较差异有统计学意义(P<0.01或P<0.05)。结论:模拟高原5000～5500m高度的气压环境每天8h低氧连续4周可形成较为理想的慢性低压低氧性肺动脉高压模型。
Objective：To establish a new kind of hypobaric and hypoxia pulmonary hypertension （HPH） model,and provide new drug screening for the clinical therapy of HPH. Method： Rats were divided into normal control group, hypoxia for 1 w group, hypoxia for 2 w group, hypoxia for 4 w group. Hypoxia was performed for 8 h every day by exposing rats （hypoxia group） to low-pressure and low-oxygen in on auto-modulating cabin （air pressure 50 kPa, oxygen concentration 10%）. Sodium pentobarbital （40 mg/kg） was injected into the abdomen of anesthetized rats and indexes for hemodynamics and right ventricular hypertrophy were measured. Morphologic changes of peripheral pulmonary artery were detected by light microscope, and the microscopic images were analyzed by using a computerized morphometric system. Result ： ① After the rats exposed to chronic hypoxia for 1 w, 2 w, or 4 w, respectively, HR and mCAP in the hypoxic group showed no great variation compared with control group. However, mPAP and RVP were significantly higher in the hypoxic group than those in the control group, and they increased progressively with the time of hypoxia. ②After hypoxia for 2 w, ratios of RV/（LV＋S） and RV/BW were significantly higher than those in 1 w hypoxic group and control group, and after hypoxia for 4w these data began significantly higher than 2 w hypoxia. ③ MT%, MA% were significantly higher in the 1 w hypoxic group than those in the control group, and they increased progressively with the time of hypoxia. Conclusion：Our study suggested that it was possible to establish a chronic hypobaric and hypoxia pulmonary hypertension model in the environment of plateau （5 000-5 500 m, 8 h/day, 4 w）.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2008年第4期297-301,共5页
Journal of Clinical Cardiology
基金
全军医药卫生科研基金军队“十一五”面上项目(No:06MA203)
国家自然科学基金面上项目(No:30370580、No:30770802)
关键词
肺动脉高压
低压低氧
动物模型
Pulmonary hypertension
Hypobaric and hypoxia
Animal model
