心房颤动患者心房组织的血管紧张素转换酶2表达及血管紧张素转换酶抑制剂干预的影响

Effects of angiotensin converting enzyme inhibitor on the expression of angiotensin converting enzyme 2 in atrium of patients with atrial fibrillation

目的探讨心房颤动(房颤)患者心房肌组织中血管紧张素转换酶2(ACE2)的表达和血管紧张素转换酶抑制剂(ACEI)干预的影响及可能的信号传导途径。方法选取接受开胸手术的风湿性心脏病患者47例,手术中取右心耳处心房肌标本。采用 RT-PCR 法检测心房肌 ACE2和 ACEmRNA 水平,采用 Western blot 法检测 ACE、ACE2、细胞外信号调节激酶1/2(ERK1/2)和磷酸化的细胞外信号调节激酶1/2(pERK1/2)蛋白表达水平,应用放射免疫法检测心房肌组织血管紧张素Ⅱ(AngⅡ)水平。结果与窦性心律组相比,持续性房颤组心房肌组织中 ACE2表达显著减少(P<0.05),而 ACE 的表达和 AngⅡ含量显著增加(P<0.05)。ERK1/2的活化水平在持续性房颤组较窦性心律组明显增加(P<0.05)。与持续性房颤组相比,ACEI 干预组 ACE2表达水平显著增加(P<0.01),ERK1/2的活化水平显著降低(P<0.05),而 ACE 表达和 AngⅡ含量差异无统计学意义。结论房颤患者心房肌组织中 ACE2表达下调,ACE/ACE2平衡失调;ACEI 对房颤的长期临床效应可能与其上调 ACE2、抑制有丝分裂素激活蛋白激酶信号途径有关。

Objective To investigate the expression of angiotensin converting enzyme 2 （ACE2） and the changes treated with angiotensin converting enzyme inhibitor （ACEI）, and its signal transduction pathway. Methods Atrial tissues were obtained from 47 patients with RHD undergoing cardiac surgery. The mRNA of ACE2 and ACE were semi-qualified by RT-PCR and normalized to the gene β-actin. Western blot analysis was employed to examine the expressions of ACE2, ACE, ERK1/2 and phosphorylated ERK （pERK1/2）. The atrial tissue angiotensin Ⅱ （Ang Ⅱ ） content was determined by radioimmunoassay detection. Results The expression of ACE2 was significantly decreased （ P 〈 0.05 ）, the expression of ACE and pERK1/2 were significantly increased （ P 〈 0.05 ）, and the level of atrial tissue Ang Ⅱ was significantly increased in patients with chronic atrial fibrillation group （CAF） compared with sinus rhythm group （SR） （ P 〈 0.05 ）. Compared with CAF patients treated without ACEI, the expression of ACE2 significantly increased （ P 〈 0.01 ） , and the relative activity of ERK1/2 significantly decreased （ P 〈 0.05 ）, whereas the expression of ACE and the level of atrial tissue Ang Ⅱ remained unchanged in CAF patients treated with ACEI. Conclusions The study suggested that the dysequilibrium of ACE/ACE2 might play an important role in the process of atrial fibrillation, which may be related to the activation of ERK1/2 pathway. The clinical effect of long-term treatment of ACEI maybe associated with elevated ACE2 expression but not ACE expression.