复氧与否对构建低氧性肺动脉高压小鼠模型的影响与比较

The effect and comparison of reoxygenation/non-reoxygenation on the establishment of mouse model for pulmonary arterial hypertension

目的:比较复氧与否对低氧联合Sugen5416构建肺动脉高压小鼠模型的异同。方法:20只,雄性,C57BL/6小鼠,采用数字表法随机分为四组(每组5只):常氧4周组、低氧(10%氧气体积分数)联合Sugen5416(20 mg/kg腹腔注射)处理3周+复氧1周组、常氧3周组、低氧联合Sugen5416处理3周组。在造模结束后采用超声仪、HE染色及PCR等方法检测各组别小鼠的肺动脉峰值流速(PA)、肺小动脉形态、右心室收缩压(RVSP)、右心室肥厚指数(RVHI)、BNP表达以及右心室室壁厚度(RVWTD)。结果:与低氧联合Sugen5416处理三周+复氧1周组小鼠相比,不复氧组小鼠的肺动脉峰值流速显著增加[(-358±43)vs.(-442±31)mm/s];肺小动脉管壁明显增厚,管腔狭窄;右心室收缩压增加[(34±5)vs.(23±3)mmHg,1 mmHg=0.133 kPa];右心室肥厚指数增加[(0.37±0.05)vs.(0.23±0.02)];脑钠肽mRNA表达水平翻倍;右心室室壁厚度增加[(0.49±0.02)vs.(0.42±0.03)mm]。结论:低氧联合Sugen5416处理3周不复氧能建立更为显著的肺动脉高压小鼠模型。

Objective:To compare the similarities and differences between the pulmonary arterial hypertension models of hypoxia combined with Sugen5416 and hypoxia combined with Sugen5416 followed by reoxygenation.Methods:totally 20 male C57BL/6 mice were randomly divided into 4 groups:3 weeks normoxia,3 weeks hypoxia(10%oxygen)combined with Sugen5416(20 mg/kg intraperitoneal injection),4 weeks normoxia and 3 weeks hypoxia combined with Sugen 5416 followed by reoxygenation for one week.After three/four weeks experiments,the morphology and peak velocity(PA)of pulmonary arterioles,right ventricular systolic pressure(RVSP),the index of right ventricular hypertrophy(RVHI),the BNP and right ventricular wall thickness during diastole(RVWTD)were assessed with ultrasonic apparatus,HE-stained,PCR and et.al.Results:Compared with the animals in hypoxia combined with Sugen5416 followed by reoxygenation,the mouse from hypoxia combined with Sugen5416 without reoxygenation showed increased PA[(-358±43)vs.(-442±31)mm/s],thickened media thickness of lung arteries with narrowed lumen,increased RVSP[(34±5)vs.(23±3)mmHg],the increased RVHI[(0.37±0.05)vs.(0.23±0.02)],doubled mRNA expression level of BNP and elevated RVWTD[(0.49±0.02)vs.(0.42±0.03)mm].Conclusions:Hypoxia combined with Sugen5416 without reoxygenation for 3 weeks can establish a more significant mouse model of pulmonary arterial hypertension.