L-精氨酸脂质体对慢性低O_2高CO_2肺动脉高压大鼠的影响

Effect of L-arginine liposome on the pulmonary hypertension in rats chronically exposed to hypoxia and hypercapnia

目的 :观察L 精氨酸 (L Arg)脂质体对慢性低氧高二氧化碳性肺动脉高压、右心室肥大大鼠的影响并探讨其机制。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 4w组 (HH组 )、低氧高二氧化碳加L Arg 4w组 (LA组 )和低氧高二氧化碳加L Arg脂质体 4w组 (LL组 )。采用化学比色法测定肺组织匀浆eNOS活性 ,用液体闪烁仪测定 [3 H] 瓜氨酸的生产量 ,计算肺动脉总一氧化氮合酶 (tNOS)的活性 ,组织原位杂交观测肺细小动脉eNOSmRNA的表达变化。结果 :①HH组平均肺动脉压力(mPAP)和右心室重量与左心室加室间隔重量比 (RV/LV +S)均高于NC组 ,LL组均明显低于LA组与HH组。②HH组的肺组织匀浆tNOS含量明显高于NC组 (P <0 .0 1) ,LL组高于LA组 (P <0 .0 5 ) ,而LA组与HH组无明显差异。③HH组的肺动脉tNOS活性显著高于NC组 (P <0 .0 1) ,而LL、LA、HH三组的tNOS活性之间均无明显差异 (P >0 .0 5 )。④HH组的肺细小动脉eNOSmRNA的平均吸光度值低于NC组 (P <0 .0 5 ) ,LA组高于HH组 (P <0 .0 5 ) ,而LL组明显高于HH组和LA组 (P均 <0 .0 1)。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右室重构的作用 ,其机制可能与L Arg脂质体促进L Arg的跨膜转运有关。

Objective:To investigate the effects and mechanism of L-arginine liposome on rats of pulmonary hypertension and hypertrophy of right ventricular chronically exposed to hypoxia-hypercapnia.Methods:Fourty male Sprague-Dawley rats were randomly divided into four groups:normal control group (NC), hypoxia-hypercapnia group (HH), hypoxia-hypercapnia + L-arginine group (LA) and hypoxia-hypercapnia + L-arginine liposome group (LL).Contents of nitric oxide synthase (NOS) in pulmonary homogenates were measured with colorimetric analysis,and L-citrulline was determined with liquid scintillometer and the activities of tNOS were counted.The change of the expression of nitric oxide synthase gene was 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 LL group were obviously lower than those of HH group and LA group.②The NOS contents in pulmonary homogenate of LL group were higher than those of LA group (P<0.05).③The tNOS activities in pulmonary arterioles were not changed among HH、LA and LL group(P>0.05). ④Situ hybridization showed the average value of integral light density (LD) of eNOS mRNA in pulmonary arterioles was significantly higher in rats of LL group than that of HH group and LA group(P<0.01).Conclusion:L-arginine liposome can lower the mPAP and lighten the remodeling of right ventricular of the rats chronically exposed to hypoxia-hypercapnia than L-arginine did. It suggests that L-arginine liposome may significantly promote the membrane transportion of L-arginine.