Alleviation of hypoxic pulmonary vascular structural remodeling by L-arginine  

L-精氨酸对低氧性肺血管结构重建的干预研究(英文)

作　　者：齐建光[1] 杜军保[1] 汪立[2] 赵斌[3] 唐朝枢[4] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学医学部,北京100083 [3]北京积水潭医院,北京100034 [4]北京大学第一医院心血管研究所,北京100034

出　　处：《Chinese Medical Journal》2001年第9期37-40,105-106,共6页中华医学杂志（英文版）

基　　金：ThisstudywassupportedbythegrantsfromtheNationalNaturalScienceFoundationofChina (No 39870 844andNo 30 0 70 796 );theMajorBasicResearchProgramofChina (No G2 0 0 0 5 6 90 5 )

摘　　要：Objective　To explore the effect of L-arginine on hypoxic pulmonary vascular structural remodeling and its possible mechanisms.Methods　Eighteen Wistar rats were randomly divided into three groups: the hypoxia group, the hypoxia with L-arginine group and the control group. Pulmonary artery mean pressure was evaluated with right cardiac catheterization. Pulmonary vascular structural changes were also observed. 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.Results　The pulmonary artery mean pressure was significantly high in hypoxic rats than in normal controls (20.33±2.18?mm?Hg vs 15.38±1.05?mm?Hg, P<0.05). Microstructural and ultrastructural analysis revealed the development of hypoxic pulmonary vascular structural remodeling in the hypoxic rats. Meanwhile, the plasma NO concentration was markedly lower in the hypoxic rats than in controls (P<0.05). The expression signals of ET-1 mRNA by pulmonary artery endothelial cells of hypoxic rats strengthened obviously. L-arginine ameliorated pulmonary hypertension (16.73±1.35?mm?Hg vs 20.33±2.18?mm?Hg, P<0.05) as well as pulmonary vascular structural remodeling in the hypoxic rats in association with an increase in plasma NO concentration (P<0.05) and inhibited ET-1 mRNA expression by the endothelial cells of pulmonary arteries.Conclusion　L-arginine might play an important role in the regulation of hypoxic pulmonary vascular structural remodeling and hypoxic pulmonary hypertension. The mechanism is probably related to promoting NO production and, as a result, inhibiting ET-1 mRNA expression by pulmonary artery endothelial cells in hypoxic rats.目的　探讨L 精氨酸 (L Arg)对低氧性肺血管结构重建的干预作用及其可能机制。方法　将 18只Wistar大鼠配伍后随机分为对照组、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明显高于对照组 (2 0 33± 2 18mmHgvs 15 38± 1 0 5mmHg ,P <0 0 5 )。低氧后大鼠肺血管显微及超微结构发生明显改变 ,肺血管结构重建形成。同时低氧组大鼠血浆NO间接含量明显低于对照组 (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PAMP较低氧组明显降低 (16 73± 1 35mmHgvs 2 0 33± 2 18mmHg ,P <0 0 5 )。L Arg缓解了低氧性肺血管结构重建的形成。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对低氧性肺血管结构重建以及低氧性肺动脉高压的形成有重要的调节作用 ,其机制可能与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?

关 键 词：L  arginine  ·   endothelin  ·   pulmonary artery  ·   hypoxia  ·   nitric oxide 

分 类 号：R363[医药卫生—病理学]