摘要
目的 探讨L 精氨酸 (L Arg)干预低氧性肺血管结构重构的机制。方法 将 18只Wistar大鼠采用区组随机法分为对照组、低氧组和低氧 +L Arg组 (共 6个配伍组 )。以右心导管法测定肺动脉压力 ,并对大鼠肺组织标本进行显微结构观测和超微结构观察 ,同时以分光光度法间接测定血浆一氧化氮 (NO)含量 ,并对肺组织以内皮素 1(ET 1)cRNA探针进行原位杂交 ,研究肺动脉内皮细胞ET 1mRNA的表达。结果 低氧组大鼠肺动脉平均压 (mPAP)为 2 .71kPa± 0 .2 9kPa ,对照组为2 0 5kPa± 0 .14kPa,两者比较P <0 .0 5。低氧组大鼠肺血管显微及超微结构发生明显改变 ,有肺血管结构重构形成。同时低氧组大鼠血浆NO间接含量为 3.5 4μmol/L± 0 .47μmol/L ,对照组为 4.79μmol/L± 0 .17μmol/L ,两者比较P <0 .0 5。低氧后肺动脉内皮细胞ET 1mRNA表达明显增强。然而 ,低氧+L Arg组大鼠mPAP为 2 .2 3kPa± 0 .18kPa ,低氧组为 2 .71kPa± 0 .2 9kPa,两者比较P <0 .0 5。L Arg缓解了低氧性肺血管结构重构的形成。同时低氧 +L Arg组大鼠血浆NO间接含量明显高于低氧组(P <0 .0 5 )。L Arg使低氧大鼠肺动脉内皮细胞ET 1mRNA表达明显受抑制。结论 L Arg通过促进低氧大鼠体内NO生成 ,从而抑制肺动脉内皮细胞ET 1mRNA表达 ,对低氧?
Objective To explore the mechanism of the therapeutic effect of L arginine on hypoxic pulmonary vascular structural remodeling. Methods Eighteen age and body weight matched Wistar rats were randomly divided into hypoxic group, hypoxic with L arginine group or control group. Pulmonary artery mean pressure ( mPAP ) of each rat was evaluated using right cardiac catheterization. Pulmonary vascular microstructure was measured and the ultrastructural changes in intra acinar pulmonary muscularized arteries were observed. Meanwhile, indirect plasma concentration of nitric oxide ( NO ) was measured via spectrophotometry, and endothelin 1(ET 1) mRNA expression in pulmonary artery endothelial cells was detected using in situ hybridization with a cRNA probe for ET 1. Results mPAP was significantly increased in hypoxic rats (2.71 kPa±0.29 kPa) as compared with that of normal controls (2.05 kPa±0.14 kPa)( P <0.05). Microstructure and ultrastructure of pulmonary arteries changed obviously in hypoxic rats with the development of hypoxic pulmonary vascular structural remodeling. Meanwhile, indirect plasma NO concentration in hypoxic rats (3.54 μmol/L±0.47 μmol/L ) was markedly decreased compared with controls (4.79 μmol/L±0.17 μmol/L)( P <0.05). The expression of ET 1 mRNA of hypoxic rats strengthened obviously. However, mPAP was significantly decreased in hypoxic rats treated with L arginine (2.23 kPa±0.18 kPa ) as compared with that of hypoxic rats (2.71 kPa±0.29 kPa) ( P <0 05). L arginine ameliorated pulmonary vascular structural remodeling of hypoxic rats in association with an increase in indirect plasma NO concentration ( P <0.05)and an inhibited ET 1 mRNA expression. Conclusion L arginine plays an important role in the regulation of development of hypoxic pulmonary vascular remodeling and hypoxic pulmonary hypertension, promoting NO production and inhibiting ET 1 mRNA expression in hypoxic rats.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2000年第3期214-218,共5页
National Medical Journal of China
基金
国家自然科学基金资助项目 !( 3 9470 73 5
3 9870 844)
