异丙肾上腺素诱导慢性心力衰竭大鼠心肌醛固酮及其核受体的变化

目的 探讨异丙肾上腺素(isoproterenol,ISO)诱导的慢性心力衰竭SD大鼠心肌醛固酮及其核受体的变化.方法 将SD大鼠抽签随机分为心力衰竭组(9只)和对照组(10只),心力衰竭组皮下注射ISO,对照组皮下注射等量生理盐水,心功能采用超声心动图及血流动力学检查,放射免疫法测定血浆及心肌组织醛固酮水平,免疫印迹和免疫组化染色法检测盐皮质激素核受体蛋白表达的变化.结果 心力衰竭组与对照组比较心功能明显下降,左心室射血分数分别为(38.8±4.0)%与(79.4±4.6)%;左心室内压最大上升速率分别为(7164.4±502.6)mm Hg(1 mm Hg=0.133 kPa)/s与(10199.5±462.9)mm Hg/s(均P＜0.01).血浆及心肌组织醛固酮含量明显升高,分别为(0.63±0.06)μg/L与(0.30±0.07)μg/L、(0.41±0.05)μg/kg与(0.08±0.01)μg/kg(均P＜0.01),左心室心肌醛固酮核受体蛋白表达增高(P＜0.01).结论 ISO可诱导SD大鼠出现类似扩张型心肌病的慢性心力衰竭表现,在这种心力衰竭模型中其循环和左心室心肌醛固酮水平明显升高,心肌醛固酮核受体表达上调,可能在心力衰竭的发生、发展中起着重要作用.

Abstract：

Objective To investigate the changes of cardiac aldosterone and mineralocorticoid receptor (MR) in Sprague-dawley (SD) rats with chronic heart failure (CHF) induced by isoproterenol (ISO). Methods The SD rats were randomly divided into CHF group (n=9) and normal control(NC) group (n=10). The experimental CHF group was induced by subcutaneous injection of ISO, and the NC group received same dose injection of sodium chloride. The heart function was evaluated with both echocardiography and hemodynamics. The contents of aldosterone in both plasma and heart were assessed by radioimmunoassay. The expression of MR was measured by Western blot and immunohistochemistry staining. Results Compared with NC group, the heart function was decreased in CHF group, the left ventricular ejection fraction was (38.8%±4.0%) in CHF and(79. 4%±4.6%), in NC group. The maximal rate of increase of ventricular pressure (+dp/dtmax) was (7164.4±502.6) mm Hg(1 mm Hg=0.133 kPa)/s in CHF and (10199.5±462.9) mm Hg/s in NC group (both P＜0. 01 ). The contents of aldosterone both in plasma and heart were higher in CHF group than in NC group (0.63±0.06)μg/L vs. (0.3±0.07) μg/L, (0.41±0.05) μg/kgvs. (0.08±0.01)μg/kg, both P＜0. 01]. The MR expression was increased in CHF group versus in NC group (P＜0.01). Conclusions The heart function is decreased in rats with CHF induced by ISO, which is similar to dilated cardiomyopathy. The higher levels of aldosterone both in circulation and in heart as and well as MR expression upregulation in heart may play important roles in the pathogenesis of CHF induced by ISO.

Changes of cardiac aldosterone and mineralocorticoid receptor in rats with chronic heart failure induced by isoproterenol

Objective To investigate the changes of cardiac aldosterone and mineralocorticoid receptor (MR) in Sprague-dawley (SD) rats with chronic heart failure (CHF) induced by isoproterenol (ISO). Methods The SD rats were randomly divided into CHF group (n=9) and normal control(NC) group (n=10). The experimental CHF group was induced by subcutaneous injection of ISO, and the NC group received same dose injection of sodium chloride. The heart function was evaluated with both echocardiography and hemodynamics. The contents of aldosterone in both plasma and heart were assessed by radioimmunoassay. The expression of MR was measured by Western blot and immunohistochemistry staining. Results Compared with NC group, the heart function was decreased in CHF group, the left ventricular ejection fraction was (38.8%±4.0%) in CHF and(79. 4%±4.6%), in NC group. The maximal rate of increase of ventricular pressure (+dp/dtmax) was (7164.4±502.6) mm Hg(1 mm Hg=0.133 kPa)/s in CHF and (10199.5±462.9) mm Hg/s in NC group (both P＜0. 01 ). The contents of aldosterone both in plasma and heart were higher in CHF group than in NC group (0.63±0.06)μg/L vs. (0.3±0.07) μg/L, (0.41±0.05) μg/kgvs. (0.08±0.01)μg/kg, both P＜0. 01]. The MR expression was increased in CHF group versus in NC group (P＜0.01). Conclusions The heart function is decreased in rats with CHF induced by ISO, which is similar to dilated cardiomyopathy. The higher levels of aldosterone both in circulation and in heart as and well as MR expression upregulation in heart may play important roles in the pathogenesis of CHF induced by ISO.