L-精氨酸对高肺血流所致肺血管结构重建的调节

目的　探讨L 精氨酸 (L Arg)对高肺血流所致肺血管结构重建的作用及其机制。方法　 2 0只Sprague Dawley大鼠随机分为对照组 (n =6 )、分流组 (n =7)和分流 +L Arg组 (n =7)。对分流组和分流 +L Arg组大鼠行腹主动脉 -下腔静脉分流术。对分流 +L Arg组大鼠每天予L Arg 1g·kg-1灌胃。 11wk后 ,以右心导管法测定肺动脉平均压(mPAP) ;检测右心室 /左心室 +室间隔 (RV/LV +S)比值 ;观测肺血管显微和超微结构的变化 ;免疫组织化学方法检测肺动脉人类尾加压素II(hUII)的表达。结果　分流组大鼠mPAP和RV/LV +S比值明显高于对照组 (P均 <0 0 1) ,并且肺动脉显微和超微结构发生明显改变。分流组大鼠肺动脉内皮细胞和平滑肌细胞hUII表达明显增强。分流 +L Arg组大鼠mPAP和RV/LV +S比值明显低于分流组 (P均<0 0 5 )。L Arg缓解了肺血管结构重建的形成 ,同时明显抑制了分流大鼠肺动脉hUII的表达。结论　L Arg抑制肺动脉内皮细胞和平滑肌细胞新型血管活性肽hUII表达 ,可能参与高肺血流所致肺血管结构重建及肺动脉高压的调节

The regulating effect of L-arginine on pulmonary vascular structural remodeling induced by high pulmonary blood flow

AIM To explore the therapeutic effect of L arginine on pulmonary vascular structural remodeling and pulmonary hypertension induced by high pulmonary blood flow and its mechanism. METHODS Twenty male SD rats were randomly divided into shunting group( n =7), shunting with L arginine group( n =7) and control group( n =6). L arginine was given into stomachs in the rats of shunting with L arginine group (1 g·kg -1 ·d -1 ). Abdominal aorta and inferior vena cava shunting was produced in rats of shunting group and shunting with L arginine group. After 11 week shunting, pulmonary artery mean pressure (mPAP) of each rat was evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass (RV/LV+S) was detected. Pulmonary vascular micro and ultra structures were examined. Meanwhile, the expression of human urotensin II (hUⅡ) by pulmonary arteries was detected by immunohistochemistry. RESULTS mPAP and RV/LV+S were significantly increased in shunting rats as compared with those of normal controls ( P <0 01, respectively). Micro structure and ultrastructure of pulmonary arteries changed obviously in shunt rats. Meanwhile, hUⅡ expression by pulmonary artery endothelial cells and smooth muscle cells was significantly augmented in rats of shunting group. However, mPAP and RV/LV+S were significantly decreased in rats of shunting with L arginine group as compared with shunt rats ( P <0 05, respectively). L arginine ameliorated pulmonary vascular structural remodeling in shunting rats in association with an inhibited hUⅡ expression. CONCLU SION L arginine plays an important role in the regulation of development of high pulmonary blood flow induced pulmonary vascular structural remodeling and pulmonary hypertension through inhibiting hUII expression in pulmonary artery endothelial cells and smooth muscle cells.