外源性CO释放分子对肺动脉高压大鼠NO及其合酶的影响

CO liberated from CORM-2 modulates on NO and nitric oxide syntheses in monocrotaline-induced pulmonary artery hypertension in rats

目的:观察外源性CO释放分子(CORM-2)对野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmona-ry artery hypertension,PAH)大鼠NO及其合酶(NOS)的影响。方法:成年雄性SD大鼠,一次性腹腔注射MCT60 mg/kg。第15天经颈内静脉插管测右心室收缩压(sRVP),筛选出肺高压模型成功大鼠40只。将这40只大鼠随机分为4组:模型组,高剂量组,低剂量组,无活性组,另取10只正常大鼠为正常对照组,共5组。第21天取各组大鼠肺组织测NO、eNOS和iNOS。结果:与对照组相比,模型组、无活性组NO明显下降(P<0.05);与模型组相比,高剂量组、低剂量组NO明显升高(P<0.01)。与对照组相比,模型组、无活性组、低剂量组eNOS明显下降,iNOS明显升高(P<0.05);与模型组相比,高剂量组、低剂量组eNOS升高,iNOS下降(P<0.01)。结论:CORM-2对PAH的治疗作用可能是通过调节eNOS、iNOS的活性进而影响NO的产生与释放来完成。

Objective： To investigate effects of CO-releasing molecules [ tricarbonyldichlororuthenium （ Ⅱ ） dimer, CORM-2 ]-liberated CO on nitric oxide （NO） and nitric oxide syntheses （eNOS/iNOS） in monocrotaline （MCT） -induced pulmonary artery hypertension （ PAH ） in rats. Methods： MCT solution was given as a single subcutaneous injection （60 mg/kg） to male Sprague Dawley rats. At the end of fifteen day, right ventricular systolic pressures （sRVP） were measured through the left jugular vein. Forty SD rats with PAH were randomly divided into 4 groups： PAH （model group）, the others received continuous administration of CORM-2 [4 mg/（kg · d）, high-dose groupl, CORM-2 [2 mg/（kg ·d） ,low-dose group], or inactive CORM-2 （inactive group） separately. In parallel 10 SD rats were taken as control group （control group）. On the twenty-first day, NO and NOS of lung tissue sections were measured by biochemical methods. Results： The NO was decreased in model and inactive groups compared with control group; while there was an increase in high-dose and low-dose groups in the lung tissue compared with model group. Compared with control group, the eNOS was decreased but the iNOS was increased significantly in model,inactive and low-dose groups. This was accompanied by a decrease in the expression of iNOS while an increase in the expression of eNOS in the lung tissue of high-dose and low-dose groups compared with model group. Conclusion ： Regulating the expression of eNOS and iNOS and influencing NO production were the possible mechanism of protecting effect of CORM-released CO modulates on PAH.