醛固酮合成酶和盐皮质激素受体基因在充血性心力衰竭心肌的表达

Expression of aldosterone synthase and mineralocorticoid receptor gene in failing human heart

目的 研究醛固酮合成酶 (Aldosterone synthase,CYP11B2 )及盐皮质激素受体 (Mineralocorticoid receptor,MR)基因在心功能不全心肌中的表达。方法 选取 2 5例行瓣膜置换术的慢性心力衰竭 (CHF)患者左心室乳头肌组织 10 0 mg,同时取 6例健康心肌组织作为对照 ,提取组织总 RNA,并逆转录为 c DNA,以特定的寡核苷酸为引物进行聚合酶链反应 ,β- actin作为内参照 ,分别观察 CYP11B2及 MR在不同心功能状态心肌中的表达。结果 在 6例正常心肌组织中 CYP11B2基因的表达为阴性 ,2 5例 CHF患者中有 10例表达阳性 ,分别为心功能 级～ 级 2例 , 级～ 级 8例 ;轻度心力衰竭患者 (心功能 ～ 级 )与重度心力衰竭患者 (心功能 ～ 级 )表达阳性率分别为 15 .4 %和 6 6 .7% ,差异有显著性 (P=0 .0 15 )。正常心肌、心功能 ～ 级和心功能 ～ 级心肌 MR/ β- actin分别为 1.2 8± 0 .13,0 .92± 0 .12 ,0 .80± 0 .2 1,与正常对照组相比 ,CHF时 MR基因表达明显下降 (P<0 .0 0 1) ,而心功能 ～ 级与心功能 ～ 级之间 ,无显著性差异 (P=0 .0 83)。慢性心力衰竭患者中 ,CYP11B2基因表达阳性与阴性组之间 MR/ β- actin表达分别为 0 .78± 0 .2 0和 0 .94± 0 .13,二者间具有显著性差异 (P=0 .0 18)。

Objective To investigate the expression level of aldosterone synthase(CYP11B2) gene and mineralocorticoid receptor (MR)gene in failing human heart. Metheods The 25 specimens came from patients with chronic congestive heart failure who had been hospitalized for operation. CYP11B2 gene and MR gene expression were detec ted by reverse transcription polymerase chain reaction(RT-PCR) methods. The function of left ventricle was assessed by echocardiography. Results CYP11B2 gene expressed in 10/25 biopsies in patients with congestive heart failure and none in 6 cases of heart tissue from normal adult. One specimen expressed CYP11B2 gene in the group of NYHA class Ⅰ, one in NYHA class Ⅱ, five in NYHA class Ⅲ and 3 expressed in NYHA class Ⅳ; CYP11B2 expressed 15.4% in the group of patients with mild heart failure(NYHA classⅠ～Ⅱ) and 66.7% in severe heart failure(NYHA class Ⅲ～Ⅳ). The expression of CYP11B2 in severe congestive heart failure was significantly hig her than that in mild heart failure(P=0.015). MR mRNA was detected in all specimens. The expression of MR gene was down-regulated in the patients with CHF. The value of MR/β-actin was 1.28±0.13, 0.92±0.12, 0.80 ±0.21 in normal adult heart , heart tissue from mild heart failure and from severe heart failure(F=16.86, P< 0.001 ), respectively. But the difference of MR/β-actin between the subgroups of CHF(NYHA classⅠ～Ⅱand NYHA class Ⅲ～Ⅳ) was not significant (P=0.08).Furthermore, the value of MR/β-actin in the myocardial tissue where CYP11B2 positively expressed was significantly lower than it in the cardial tissue where CYP11B2 negatively expressed(P=0.018).Conclusion CYP11B2 gene expression is activated in the severe congestive heart failure, while MR gene expression is down-regulated in CHF. The activation of CYP11B2 gene is associated with the severe left ventricular dysfunction in human CHF.