夹竹桃麻素对高肺血流肺动脉高压大鼠的治疗作用

目的 观察夹竹桃麻素(apocynin)对肺高血流肺动脉高压大鼠肺动脉内皮细胞活性氧(ROS)及NADPH氧化酶4(NOX4)蛋白水平的影响,研究Apocynin对肺高血流肺动脉高压形成的拮抗作用.方法 将30只雄性SD大鼠随机均分为对照组、分流给药组、分流组,通过腹主动脉-下腔静脉分流法建立左向右分流肺高血流肺高压大鼠模型,测定大鼠平均肺动脉压、肺小动脉中膜厚度百分比(WT％)、肺小动脉管壁面积百分比(WA％);体外培养模型大鼠肺动脉内皮细胞,流式细胞仪检测2,7一二氢二氯荧光黄双乙酸钠(DCFH- DA)荧光探针标记的肺动脉内皮细胞活性氧水平,Western Blot法检测大鼠肺动脉内皮中NOX4蛋白的表达情况.结果 与分流组对比,分流给药组大鼠肺动脉压升高和肺血管重构情况明显改善,肺动脉内皮细胞中NOX4蛋白的表达较分流组虽无明显减少,但细胞内ROS的水平显著下降.结论 持续使用夹竹桃麻素干预,可使左向右分流肺动脉高压大鼠肺动脉内皮细胞中ROS水平明显下降,从而拮抗大鼠肺动脉高压的形成.

Therapeutic Effect of Apocynin to Rat with Pulmonary Hypertension Caused by High Pulmonary Blood Flow

Objective To observe the effect of apocynin to nicotinamide adenine dinucleotide phosphate-oxidase（NOX4）protein and reactive oxygen species（ROS）level in rat pulmonary artery endotheliocyte and to explore the antagonism of apocynin to formation of pulmonary hypertension.Methods Thirty male SD rats used in the experiment were randomly divided into three groups：control group,shunt-apocynin group and shunt group.We established the model by abdominal aorta-inferior vena cava shunt.WT,WA and mPAP of rats were measured.Pulmonary artery endotheliocyte of rat was cultured.ROS of endotheliocyte was detected by flow cytometry and expression of NOX4 protein in endotheliocyte was tested by Western blot.Results With the intervention of apocynin,elevation of mPAP and pulmonary artery remodeling in shunt-apocynin group were inhibited significantly comparing with the shunt group.The expression of NOX4 protein was not reduced evidently,but ROS level of endotheliocyte was decreased significantly in the shunt-apocynin group.Conclusion Persistent apocynin intervention can reduce the level of ROS in pulmonary artery endotheliocyte of rat with left to right shunt,thus can inhibit the formation of pulmonary hypertension in model rat.