钙通道阻滞剂对缺氧大鼠右心室心肌CnAβmRNA及血浆NO、iNOS、ET-1水平的影响

Effect of Ca^(2+) channel blocker on the levels of myocardial calcineurin AβmRNA in right ventricle and plasma NO,nitric oxide synthase and endothelin-1 in rats with chronic hypoxia

目的通过研究钙通道阻滞剂对缺氧大鼠右心室心肌钙调神经磷酸酶Aβ(CnAβ)mRNA及血浆NO、一氧化氮合酶(iNOS)、内皮素-1(ET-1)水平的影响,进一步探讨钙通道阻滞剂防治慢性缺氧致右心室肥大的机制。方法实验大鼠分为3组,采用配伍组设计,每组各10只,即正常组、缺氧组、苯磺酸氨氯地平(Norvasc)处理组(灌喂Norvasc 30 mg.kg-1.d-1),后2组置于氧浓度为(10.0±0.5)%的大型玻璃舱中,持续缺氧21 d。第21天处死大鼠,采血测NO、iNOS、ET-1的水平,分离心脏称质量,并留右心室测CnAβmRNA的表达。结果⑴缺氧组右室与左室加室间隔的重量比、右室重量与体重之比均明显高于正常组和处理组(P<0.01)。⑵缺氧组右心室心肌CnAβmRNA的表达明显高于正常组和处理组(P<0.01)。⑶缺氧组血浆NO、iNOS水平明显低于正常组和处理组(P<0.01),ET-1水平则明显高于正常组和处理组(P<0.01)。结论钙通道阻滞剂-Norvasc能够抑制慢性缺氧右心室肥大,也可能与调节血浆NO、iNOS、ET-1水平,改善肺动脉压力,下调CnAβmRNA的表达有关。

Objective Many studies showed that Ca^2＋ channel blocker could prevent and treat right ventricular hypertrophy （RVH） induced by chronic hypoxia. To further identify the mechanism, we investigated the effect of Ca^2＋ channel blocker on the levels of myocardial calcineurin AβmRNA（CnAβ） in RV and plasma nitric oxide （NO）, NO synthase and endothelin-1 （ET-1） in rats with chronic hypoxia. Methods 30 rats were divided into three groups by randomized block design： treatment group with Amlodipine Besylate ablets [ （30 mg·kg^-1·d^-1） , administered via garage] , chronic： hypoxia group, and control group. The rats in treatment group and chronic hypoxia group were exposed to normobaric chronic hypoxia [ （ 10.0 ± 0. 5 ） % 02 ] for 21 days. On the 21st day of experiment, all rats were sacrificed and the hearts were collected for measuring the weight. Blood samples were also drawn from the ventricles for measuring plasma NO, iNOS and ET-1 levels. CnAβmRNA levels in RV were measured by RT-PCR. Results （1）The RV/（ LV ＋ S） ,RV/BW ratios were significantly higher in chronic hypoxia group than those of control group and treatment group（ P 〈 0. 01 ） ; （2）RV CnAβmRNA levels in chronic hypoxia group were higher than those of treatment group and normal control group （ P 〈0. 01 ） ; （3） The levels of plasma NO, iNOS were significantly lower in chronic hypoxia group than those of control group and treatment group, however, the levels of ET-1 were significantly higher in chronic hypoxia group than those of control group and treatment group （ P 〈0. 01 ）. Conclusion Ca^2＋ channel blocker （ Amlodipine Besylate） effectively inhibited RVH induced by chronic hypoxia, which might be related to its function of modulating＇the levels of NO, iNOS, and ET-1 in plasma, relieving the pulmonary hypertension and decreasing the levels of CnAβmRNA in RV.