L-精氨酸对高肺血流量大鼠肺动脉平滑肌细胞增殖与凋亡的影响

Effect of L-arginine on the proliferation and apoptosis of pulmonary artery smooth muscle cells in rats with high pulmonary flow

探讨L 精氨酸 (L Arginine ,L Arg)对高肺血流量所致肺动脉高压平滑肌细胞增殖与凋亡的干预作用。 18只雄性SD大鼠随机分为对照组、分流组和分流 +L 精氨酸 (L Arg)组。对分流组和分流 +L Arg组大鼠行腹主动脉 下腔静脉分流术。观察术后 11周大鼠肺动脉平均压 (mPAP)和右心室肥厚的改变 ,采用免疫组织化学方法研究肺动脉平滑肌细胞PCNA和Fas的表达 ,并通过原位缺口末端标记方法 (TUNEL)检测大鼠肺动脉平滑肌细胞的凋亡。结果表明分流组大鼠mPAP、右心室 (RV)与左心室加室间隔 (LV +S)的比值 ,肺中、小型动脉平滑肌细胞增殖指数(PI) ,凋亡指数 (AI) ,PI AI比值明显高于对照组大鼠 (P <0 0 5 ) ,同时 ,分流后肺动脉平滑肌细胞Fas表达增高。然而 ,分流 +L 精氨酸组大鼠mPAP、RV LV +S明显低于分流组 (P <0 0 5及 0 0 1) ,并且L Arg减少了肺中、小型动脉平滑肌细胞的增殖 ,促进了凋亡 (P <0 0 1) ,wviycL Arg组大鼠PI AI比值较分流组明显降低 (P <0 0 1) ,同时 ,L Arg使分流大鼠肺动脉平滑肌细胞Fas表达明显增强。以上结果提示 ,L 精氨酸通过抑制肺动脉平滑肌细胞的增殖 ,促进其凋亡 ,从而对高肺血流量所致肺动脉高压的形成有重要的调节作用。

To explore the therapeutic effect of L-arginine on proliferation and apoptosis of pulmonary artery smooth muscle cells (SMC) in high pulmonary blood flow-induced pulmonary hypertension. Abdominal aorta and inferior vena cava shunting was constructed in rats of shunt group and shunt with L-arginine group. After 11-week-shunting, pulmonary artery mean pressure (mPAP) and the hypertrophy of right ventricle of each rat were evaluated. Immunohistochemistry for PCNA, Fas expressions and TUNEL (TdT-mediated dUTP-biotin nick and labeling) were examined to identify cell proliferation and apoptosis. We found the mPAP, proliferative index (PI), apoptotic index (AI) and the ratio of PI/AI of pulmonary artery SMC in shunt group elevated obviously compared with those of control group (P<0.01). Meanwhile, the expressing integral score of Fas in shunt group elevated (P<0.01). However, L-arginine reduced mPAP, PI and again augmented AI as well as the expressing integral score of Fas of pulmonary artery SMCs. The ratio of PI/AI was significantly reduced in rats of shunt with L-arginine group. The result showed that L-arginine inhibited proliferation and promoted apoptosis of pulmonary artery SMC in shunt rats, which might provide theoretical basis for the therapy of the high pulmonary blood flow-induced pulmonary hypertension.