L-精氨酸脂质体对慢性低氧高二氧化碳大鼠一氧化氮及其合酶基因表达的影响

EFFECT OF L-ARGININE LIPOSOME ON NITRIC OXIDE CONTENT AND NITRIC OXIDE SYNTHASE GENE EXPRESSION IN RATS CHRONICALLY EXPOSED TO HYPOXIA AND HYPERCAPNIA

目的 :探讨L 精氨酸脂质体 (L Arg)对慢性低氧高二氧化碳大鼠一氧化氮代谢及内皮型一氧化氮合酶基因(ecNOSmRNA)表达的影响。方法 :将 4 0只健康雄性SD大鼠随机分为 4组 ,正常对照组 (NC组 ) ,低氧高二氧化碳 4周组 (HH组 ) ,低氧高二氧化碳加L Arg4周组 (HL组 )和低氧高二氧化碳加L Arg脂质体 4周组 (HP组 )。采用硝酸还原酶法测定血浆一氧化氮代谢产物 (NOx-)含量 ,组织原位杂交、光镜和图像分析等方法观察肺细小动脉显微结构以及肺细小动脉ecNOSmRNA的表达变化。结果 :①HH组mPAP和RV/ (LV +S)高于NC组 ,HP组均明显低于HL组与HH组 ;②HH组的血浆NO含量显著低于NC组 (P <0 .0 1) ,HL组与HP组均明显高于HH组(P <0 .0 1) ;③HH组的肺细小动脉ecNOSmRNA的平均吸光度值低于NC组 (P <0 .0 5 ) ;而HP组明显高于HH组和HL组 (P <0 .0 1) ;④HP组的肺细小动脉管壁面积 /管总面积比值 (WA/TA)和中膜厚度 (PAMT)均明显低于HH组 (P <0 .0 1) ,且低于HL组 (P <0 .0 5 )。结论 :L Arg脂质体较L Arg有更明显的降低慢性低氧高二氧化碳大鼠肺动脉压和减轻肺血管重建的治疗作用 ,其机制可能与L Arg脂质体促进L Arg的跨膜转运有关。

Aim: To investigate the effects of L-arginine liposome on nitric oxide(NO) and nitric oxide synthase gene (NOS mRNA) in rats chronically exposed to hypoxia-hypercapnia. Methods: Fourty male SD rats were randomly divided into four groups(n=10):normal control group(NC), hypoxia-hypercapnia group (HH), hypoxia-hypercapnia + L-arginine group(HL) and hypoxia-hypercapnia + L-arginine liposome group (HP).Contents of NO in plasma were measured using colorimetric analysis. Expression of nitric oxide synthase gene were measured with situ hybridization. Results: ①The mean pulmonary artery pressure(mPAP) and weight ratio of right ventricle to left ventricle and septum(RV/LV+S) of HP group were obviously lower than those of HH group and HL group.②The NO contents in plasma of HP group were obviously higher than those of HH group and HL group(P<0.01).③Situ hybridization showed the average value of integral light density(LD) of ecNOS mRNA in pulmonary arterioles was significantly higher in rats of HP group than that of HH group and HL group(P<0.01).④Light microscopy showed WA/TA (vessel wall area/total area) and PAMT (media thickness ratio of pulmonary arterioles) were significantly lower in rats of HP group than those of HH group(P< 0.01).Conclusion: L-arginine liposome could lower the mPAP and lighten the remodeling of pulmonary arterioles of the rats chronically exposed to hypoxia-hypercapnia than L-arginine does. It suggests that L-arginine liposome significantly promotes the membrane transportion of L-arginine.