L-精氨酸调节左向右分流所致肺动脉高压大鼠胶原代谢的研究

目的　探讨L 精氨酸 (L Arg)对高肺血流量所致肺动脉高压大鼠肺动脉胶原代谢的干预作用及其机制。方法　在大鼠行腹主动脉 下腔静脉分流造成的肺动脉高压模型基础上 ,给予L Arg灌胃 (1g·kg-1·d-1,11周 )。 11周后 ,观察肺血流动力学 ,采用免疫组织化学法检测大鼠肺动脉Ⅰ、Ⅲ型胶原蛋白的表达 ,以原位杂交法检测Ⅰ、Ⅲ型前胶原蛋白α1(Ⅰ )mRNA、α1(Ⅲ )mRNA、基质金属蛋白酶 1(MMP 1)mRNA、抑制胶原降解作用的中性蛋白酶组织抑制剂 1(TIMP 1)mRNA的表达。结果　分流 11周后 ,肺动脉高压形成。分流组大鼠肺中、小型肺动脉中Ⅰ、Ⅲ型胶原、α1(Ⅰ )、α1(Ⅲ )前胶原mRNA表达与对照组比较明显增加 ,同时TIMP 1mRNA、MMP 1mRNA表达、TIMP 1/MMP 1比值明显高于对照组 (P <0 .0 1)。然而 ,L Arg明显缓解了分流组大鼠肺动脉高压。分流 +L Arg组大鼠肺中、小型肺动脉中Ⅰ、Ⅲ型胶原、α1(Ⅰ )、α1(Ⅲ )前胶原mRNA表达较分流组明显降低 ,且TIMP 1mRNA、MMP 1mRNA表达、TIMP 1/MMP 1比值较分流组显著降低 (P值均 <0 .0 5 )。结论　L Arg通过减少细胞外基质 胶原的堆积 ,增加其降解 ,从而对高肺血流量所致肺动脉高压及肺动脉血管结构重建的形成有重要的调节作用。

The modulating effect of L-arginine on collagen metabolism of pulmonary artery in pulmonary hypertension induced by a left-to-right shunt

OBJECTIVE: To explore the modulating effect of L-arginine on collagen metabolism of pulmonary artery in rats with high pulmonary blood flow-induced pulmonary hypertension and its molecular mechanism. METHOD: Eighteen rats were randomly divided into 3 groups of 6 rats: shunt group (pulmonary hypertension was established with an abdominal aorta and inferior vena cava shunting), shunt + L-Arg group (L-arginine, 1 g x kg(-1) x d(-1) was given into the stomachs of rats for weeks after shunting), and control group. After 11 weeks of experiment, the pulmonary hemodynamics were studied, the contents of collagen I and collagen III expressions were detected by immunohistochemical assay. The expressions of procollagen I mRNA, procollagen III mRNA, TIMP-1 mRNA and MMP-1 mRNA were detected by in situ hybridization. RESULTS: After 11 weeks of experiment, the mean pulmonary artery pressure (MPAP) in shunt group was 23.0 mm Hg +/- 0.9 mm Hg, higher than that in shunt + L-Arg group (18.0 mm Hg +/- 1.8 mm Hg, P < 0.01) and that in control group (15.7 mm Hg +/- 1.1 mm Hg, P < 0.01). The expressing integral scores of collagen I and collagen III, the expression of procollagen I mRNA, Procollagen III mRNA, TIMP-1 mRNA, MMP-1 mRNA and the ratio of TIMP-1/MMP-1 were significantly higher in the shunt group than in the other 2 groups (P < 0.01 or P < 0.05). CONCLUSION: L-arginine reduces the synthesis of extracellular matrix-collagen and increases its degradation. Thus L-arginine has important modulating effects on pulmonary hypertension and pulmonary vascular remodeling induced by high pulmonary blood flow.