ACEI对风湿性心脏病心房颤动患者心房ACE、ERK表达和纤维化改变的影响

Effects of ACEI on the expression of ACE and ERK and the changes of atrial fibrosis in patients with atrial fibrillation

目的:研究风湿性心脏病(风心病)心房颤动(房颤,AF)患者用血管紧张素转换酶抑制剂(ACEI)时心房组织血管紧张素转换酶(ACE)、细胞外信号调节激酶(ERK)表达与心房纤维化改变。方法:35例风心病二尖瓣狭窄接受外科手术患者,手术时取右心耳处心房组织4 0 0mg ,通过逆转录—聚合酶链反应技术,以GAPDH为内参照,测量ACE ,ERK2mRNA变化,用WesternBlotting观察ACE、磷酸化ERK( pERK)在蛋白水平表达的差异,经Masson染色研究胶原纤维容积分数(CVF)改变情况。结果:与窦性节律患者比较,慢性房颤患者在mRNA水平上ACE、ERK2表达上调,在蛋白水平上ACE、pERK表达上调(P <0 .0 1或P <0 .0 5 ) ,CVF也显著增加(P <0 .0 1) ;与未应用ACEI组比较,用ACEI组ERK2mRNA、pERK蛋白表达下调(P <0 .0 5 ) ,ACE表达无差异,CVF虽有减少趋势,但无统计学意义(P >0 .0 5 )。结论:风心病慢性房颤患者较窦性节律患者ACE、ERK表达增加,纤维化加重;而在应用ACEI的慢性房颤患者,ERK2 ,pERK表达有显著下降,纤维化减轻,说明在房颤时,局部激活的肾素—血管紧张素系统(RAS)经ERK途径介导了心房纤维化。

Objective:To study the expression of angiotensin-converting enzyme(ACE),extracellular signal-regulated kinase(ERK),and the changes of atrial fibrosis in patients with rheumatic heart disease(RHD) and atrial fibrillation(AF) treated with angiotensin-converting enzyme inhibitor(ACEI).Methods:Atrial tissues were obtained from the right appendage during open surgery in 35 patients with RHD.The mRNA of ACE and ERK2 were semi-qualified by reverse transcription-ploymerase chain reaction(RT-PCR) and normalized to the glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Western blotting analysis was employed to examine the expressions of ACE and phosphorylated ERK(pERK).Atrial collagen volume fraction(CVF) was detected by Masson's stain.Results:The mRNA of ACE and ERK2 or the protein of ACE and pERK were significantly increased,and CVF was significantly increased in patients with chronic atrial fibrillation(CAF) compared with sinus rhythm group(SR)( P <0.01 or P <0.05).Compared with CAF patients treated without ACEI,the mRNA of ERK2 and protein of pERK were significantly decreased in CAF patients treated with ACEI( P <0.05),but there was no difference in ACE,and decrease in CVF was not statistically significant( P >0.05).Conclusion:The expressions of ACE,ERK2 and pERK increase,and fibrosis is more severe in RHD patients with CAF as compared with those with SR.Compared with CAF patients treated without ACEI,the expressions of ERK2 and pERK significantly decrease( P <0.05) and decrease in CVF is detected( P >0.05)in CAF patients treated with ACEI.This suggests that the increasing expression of ERK2 and pERK resulting from local renal angiotensin-converting enzyme system activation mediates the development of atrial fibrosis,and ACEI may contribute to lesser atrial fibrosis in RHD patients with AF.