左旋精氨酸对大鼠心脏移植物血管病变的抑制作用

Inhibitory effect of L-arginine on cardiac allograft vasculopathy in a rat cardiac allograft model

目的 研究左旋精氨酸对大鼠心脏移植物血管病变的抑制作用及其机理。方法 采用大鼠异位心脏移植模型。对照组 :移植后不用左旋精氨酸 ;实验组 :移植后按 80 0mg·kg-1·d-1将左旋精氨酸加入饮水中。于移植后 2个月和 3个月检测各组的心脏移植物 ,血管病变评分和血浆一氧化氮含量。结果 移植后 2个月 ,实验组的移植物存活率为 90 .5 % ,显著高于对照组的 6 1.5 % (P <0 .0 5 )。移植后 2个月和 3个月 ,实验组血浆一氧化氮含量均显著高于对照组 ,分别为 ( 10 5 .37± 10 .6 6 ) μmol/Lvs( 6 8.5 4± 6 .83) μmol/L(P <0 .0 5 ) ,和 ( 10 4.5 3± 12 .31) μmol/Lvs ( 6 6 .32± 10 .5 4) μmol/L(P <0 .0 5 ) ;而对照组心脏移植物血管病变评分显著高于实验组 ,分别为 2 .4± 0 .7vs 1.1± 0 .6 (P <0 .0 5 ) ,和 3.0±0 .8vs 1.6± 0 .9(P <0 .0 5 )。实验组心脏移植物的冠状动脉内膜病变轻微 ,内皮和内弹力层基本保持完整 ,平滑肌细胞增殖不明显。结论 补充左旋精氨酸可改善心脏移植物血管病变 ,其机理与一氧化氮合成增加有关。一氧化氮具有保持内皮功能 ,抑制平滑肌细胞增殖的作用。

Objective To explore the inhibitory effect of L-arginine on cardiac allograft vasculopathy (CAV) and its possible mechanisms.Methods The rat cardiac allograft model was used. In the control group (n=26), L-arginine was not administered after heterotopic cardiac transplantation, and the other 21 rats (experimental group) received administration of L-arginine ( 800?mg/kg every day, in drinking water) after heart transplantation. CAV score was evaluated and plasma nitric oxide (NO) was measured at 2 and 3 months after transplantation. Results Graft survival rate 2 months after transplantation was significantly (P< 0.05) higher in experimental group (19 of 21, 90.5?%) than that in control group (16 of 26, 61.5?%). The plasma NO level was significantly higher in experimental group than in control group both at 2nd month ( 105.37± 10.66?)μmol/L vs ( 68.54± 6.83?)μmol/L, (P< 0.05) and 3rd month ( 104.53± 12.31)?μmol/L vs ( 66.32± 10.54?)μmol/L, (P< 0.05) after transplantation. CAV score was significantly higher in control group than in experimental group both at 2nd month 2.4± 0.7?vs 1.1± 0.6, (P< 0.05) and 3rd month 3.0± 0.8?vs 1.6± 0.9, (P< 0.05) after transplantation. The cardiac allografts in experimental group showed minimal intimal proliferation, the endothelium and internal elastic lamina remained almost intact, and reduced smooth muscle cell proliferation.Conclusions Dietary L-arginine attenuated CAV. The protective effect may be related to the generation of NO to maintain endothelial function and direct inhibit smooth muscle cell proliferation.