L-精氨酸调节大鼠低氧性肺血管结构重建与肺动脉平滑肌细胞凋亡

目的:探讨L-精氨酸(L-arginine,L-Arg)对低氧性肺血管结构重建大鼠肺动脉平滑肌细胞凋亡的影响及其机制.方法:将17只Wistar大鼠随机分为对照组(n=7)、低氧组(n=5)和低氧+L-Arg组(n=5).对大鼠肺血管进行显微形态学观测.通过末端转移酶介导的dUTP切口末端标记法(TUNEL)检测肺动脉平滑肌细胞凋亡,并以免疫组织化学方法研究肺动脉平滑肌细胞Fas表达.结果:低氧2周后出现大鼠肺血管结构重建.同时,肺中、小型动脉凋亡平滑肌细胞百分数均明显低于对照组(P均＜0.05),平滑肌细胞Fas表达明显降低.然而,L-Arg缓解了低氧性肺血管结构重建的形成.低氧+L-Arg组大鼠肺中、小型动脉凋亡平滑肌细胞百分数均明显高于低氧组(P均＜0.05).L-Arg使低氧大鼠肺动脉平滑肌细胞Fas表达明显增强.结论:L-Arg通过使肺动脉平滑肌细胞Fas表达上调,促进肺动脉平滑肌细胞的凋亡,从而对低氧性肺血管结构重建有重要的调节作用.

L-arginine regulates hypoxic pulmonary vascular structural remodeling and pulmonary artery smooth muscle cell apoptosis in rats

Objective: To explore the impact of L arginine ( L Arg ) on apoptosis of smooth muscle cells in pulmonary arteries of the rats with hypoxic pulmonary vascular structural remodeling. Methods: Seventeen Wistar rats were randomly divided into hypoxia group ( n =5 ), hypoxia with L arginine group ( n =5 ) and control group ( n =7 ). Pulmonary vascular microstructure was measured under a light microscope. Apoptotic smooth muscle cells in pulmonary arteries were detected by TdT mediated dUTP biotin nick end labeling ( TUNEL ), and the expression of Fas protein by pulmonary artery smooth muscle cells was detected using immunohistochemistry technique. Results: Pulmonary vascular structural remodeling developed after 2 week hypoxia. Meanwhile, the percentage of apoptotic smooth muscle cells in pulmonary arteries was markedly decreased in hypoxic rats compared with normal controls ( P <0.05 ). The expression of Fas protein of hypoxic rats was inhibited obviously. L arginine ameliorated pulmonary vascular structural remodeling of hypoxic rats in association with an increase in the percentage of apoptotic smooth muscle cells in pulmonary arteries and a strengthened Fas expression by pulmonary artery smooth muscle cells. Conclusion: L arginine plays an important role in the regulation of development of hypoxic pulmonary vascular structural remodeling throughpromoting Fas expression and thereby apoptosis in pulmonary artery smooth muscle cells.