快速起搏致充血性心力衰竭犬肺组织内皮素系统表达的变化

Expression of endothelin system in pulmonary tissue in a canine pacing-induced congestive heart failure model

目的 :观察充血性心力衰竭犬肺组织内皮素系统表达的变化。方法 :采用快速右心室起搏致心力衰竭犬模型 ,2 1只犬随机分为对照组、起搏 2周组和起搏 4周组。测定血液动力学评价心衰严重程度 ,RIA法测定血浆内皮素浓度 ,RT -PCR法定量检测肺组织内皮素系统mRNA的表达水平。结果 :起搏 2周组和起搏 4周组犬血浆内皮素水平显著高于对照组 ,肺组织内皮素前体原 - 1的表达比较显示 ,起搏 4周组明显高于起搏 2周组 (0 .5 3± 0 0 8vs0 3 5± 0 0 8,P <0 0 1) ,起搏 2周组明显高于对照组 (0 3 5± 0 0 8vs 0 14± 0 0 6,P <0 0 1)。内皮素前体原 - 1表达与心力衰竭的严重程度明显相关。起搏 2周组中内皮素A受体表达明显高于对照组 ,而内皮素B受体表达低于对照组。 2组心衰犬内皮素A受体和B受体比例均明显高于对照组 ,而起搏 4周组明显高于起搏 2周组。结论 :在充血性心力衰竭犬模型中 ,肺组织内皮素的过度表达及其受体表达的变化可能是血浆内皮素上升的主要原因之一 。

AIM: To evaluate expression of the components of endothelin system in pulmonary tissue in a canine pacing-induced congestive heart failure model. METHODS: Twenty-one dogs were divided into 3 groups received 2 (pacing 2 group) or 4 weeks (pacing 4 group) rapid right ventricular pacing, respectively, whereas the other group consisted of 7 dogs received sham-operation as control group. Haemodynamic parameters were detected via left and right heart catheterization. Plasma endothelin-1 was determined by means of RIA. In addition, RT-PCR was used to quantify expression of mRNA of components of endothelin system using β-actin as internal control. One-way ANOVA and linear regression analysis were used for statistical study. RESULTS:Plasma endothelin-1 increased significantly in heart failure animals. The ratio of preproET-1 to β actin mRNA was significantly increased from 0.14±0.06 in control group to 0.35±0.08 in pacing 2 group and 0.53±0.08 in pacing 4 group ( P< 0.01). Expression of preproET-1 was correlated to variables of heart failure and pulmonary hypertension significantly. Expression of ETA mRNA in pacing 4 group increased significantly. In the contrast, expression of ETB mRNA in pacing 4 group decreased. Thus the ratio of ETA to ETB in both paced groups increased significantly compared with control group, whereas that of pacing 4 group was higher than pacing 2 group. CONCLUSIONS: These results suggested that endothelin system might play a pathophysiological role in the secondary pulmonary hypertension in heart failure. Overexpression of endothelin and alteration of expression of its receptors might be a possible source of elevated plasma ET-1 in this canine congestive heart failure model.