肾上腺髓质素对高肺血流大鼠肺组织氧化应激的调节作用

发布时间：2018-05-06 15:27

本文选题：肺动脉高压 + 高肺血流　；参考：《中国病理生理杂志》2017年04期

【摘要】：目的:研究肾上腺髓质素(ADM)对高肺血流性肺动脉高压大鼠肺组织氧化应激的调节作用及其机制。方法:健康雄性SD大鼠随机分为对照组、分流组和分流+ADM组。对后2组大鼠行腹主动脉-下腔静脉分流术。8周后,对分流+ADM组大鼠皮下埋微量渗透泵持续予ADM 1.5μg·kg~(-1)·h~(-1)。继续饲养2周后,右心导管法测定平均肺动脉压(mPAP)和右心室/(左心室+室间隔)重量比值,检测肺中、小肌型动脉相对中膜厚度(RMT),比色法测定肺组织匀浆丙二醛(MDA)含量、总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性和谷胱甘肽过氧化物酶(GSH-Px)活性,Western blot法检测肺组织还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶4(NOX4)的表达。结果:与对照组相比,分流组大鼠的mPAP、右心室肥厚程度以及肺中、小肌型动脉RMT均明显增加,肺组织MDA含量明显升高,T-AOC、SOD活性和GSH-Px活性均明显降低,肺组织NOX4表达明显升高。ADM使肺动脉压力明显回降,右心室肥厚程度减轻,肺血管结构改变缓解,肺组织MDA含量明显下降,T-AOC、SOD活性和GSH-Px活性明显升高,肺组织NOX4表达明显降低。结论:ADM能够抑制大鼠高肺血流性肺动脉高压和肺血管结构重构形成中的氧化应激反应,作用机制可能与其下调肺组织NOX4表达以及增强抗氧化活性有关。
[Abstract]:Aim: to investigate the effects of adrenal medullary hormone (ADM) on oxidative stress in pulmonary tissue of rats with high pulmonary flow induced pulmonary hypertension. Methods: healthy male SD rats were randomly divided into control group, shunt group and shunt ADM group. The rats in the latter two groups were treated with abdominal aorta-inferior vena cava shunt for 8 weeks. The rats in shunt ADM group were continuously treated with ADM 1.5 渭 g / kg 路h ~ (-1) 路L ~ (-1) 路kg ~ (-1) 路h ~ (-1). After 2 weeks of feeding, the mean pulmonary artery pressure (MPAP) and the right ventricular septal weight ratio (RVS) were measured by right cardiac catheterization, the relative medial thickness of arterioles and the content of malondialdehyde (MDA) in lung homogenate were measured by colorimetric method. Total antioxidant activity (T-AOC), superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity. The expression of reduced nicotinamide adenine dinucleotide phosphatase (NADPH) oxidase 4NOX4 was detected by Western blot. Results: compared with the control group, the mPAPs, the degree of right ventricular hypertrophy and the RMT in the pulmonary arterioles of shunt rats were significantly increased, while the content of MDA in lung tissue was significantly increased, and the activity of SOD and GSH-Px in lung tissue were significantly decreased. The expression of NOX4 in lung tissue was significantly increased. ADM significantly decreased pulmonary artery pressure, decreased the degree of right ventricular hypertrophy, alleviated pulmonary vascular structure, decreased the content of MDA in lung tissue and increased the activity of GSH-Px and T-AOC, and decreased the expression of NOX4 in lung tissue. Conclusion: NOX4 can inhibit oxidative stress in pulmonary hypertension and pulmonary vascular remodeling in rats, which may be related to its down-regulation of NOX4 expression and enhancement of antioxidant activity.
【作者单位】：北京大学第一医院儿科;山西省儿童医院呼吸科;
【基金】：国家自然科学基金资助项目(No.30973226)
【分类号】：R544.1

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