心房颤动患者心房肌组织醛固酮水平和CYP11B2基因与心房结构重构研究

Aldosterone in local atria, CYP11B2 mRNA expression and atrial structural remodeling in patients with atrial fibrillation

目的探讨心房颤动(房颤)患者心房肌组织醛固酮水平和醛固酮合成酶基因CYP11B2 mRNA表达与房颤时心房结构重构的关系。方法入选进行人工心脏瓣膜置换术的风湿性心脏瓣膜病患者25例,其中窦性心律者12例,慢性房颤(≥6个月)者13例。上述患者均于术前行经胸超声心动图检查并留取相关资料,于手术时同时取左右心房侧壁组织。用放射免疫法测定心房组织醛固酮水平;用VG染色法对胶原容量分数(CVF)半定量分析;实时荧光定量PCR测定CYP11B2 mRNA在心房肌组织中的表达情况。结果与窦性心律组比较,房颤组左心房内径显著扩大(P<0．01);心房肌组织醛固酮水平和CVF均明显增加(P均<0．001);心房肌组织CYP11B2 mRNA表达也明显增加(P< 0．001);上述指标无论是在窦性心律时还是在房颤时其在左右心房之间差异无统计学意义(P均> 0．05)。CVF和左心房内径显著正相关(r=0．845,P<0．001);心房组织醛固酮水平与左心房内径(r= 0．814,P<0．001)和CVF(r=0．885,P<0．001)均呈明显正相关;CYP11B2 mRNA表达量和CVF亦呈明显正相关(r=0．757,P<0．001)。结论心房颤动时心房结构重构与其组织醛固酮水平增加和CYP11B2 mRNA表达增加有关,醛固酮受体拮抗剂可能在阻止房颤的心房结构重构进程上发挥治疗作用。

Objective To investigate aldosterone in local atria, the mRNA expression of aldosterone synthase CYPI 1 B2 and atrial structural remodeling in patients with chronic atrial fibrillation, and to find the association of these factors. Methods Twenty-five patients with rheumatic heart valve disease, 12 patients in si- nus rhythm and 13 in chronic atrial fibrillation（≥6 months）,underwent transthoracic echocardiography. Right and left atrial lateral wall tissue samples were obtained simultaneously from these patients during mitral/aortic valve replacement operation. Radioimmunoassay was used to determine aldosterone in local atria and collagen volume fraction （CVF） was analyzed by VG staining. The mRNA expression of aldosterone synthase CYPI 1 B2 in atrial myocardium was determined by using realtime quantitative PCR. Results The left atrial diameters increased markedly in atrial fibrillation group as compared to sinus rhythm group（P 〈0. 01 ）. Compared with that of sinus rhythm groups, the aldosterone in local atria was increased significantly in atrial fibrillation group（ P 〈 0. 001 ）. VG staining revealed that CVF increased significantly in atrial fibrillation groups compared with that in sinus rhythm group（ P 〈 0. 001 ）. And the level of mRNA of CYPI 1 B2 was increased greatly in atrial fibrillation groups compared with that in sinus rhythm（ P 〈0. 001 ）. But the aldosterone, CVF and the mRNA expression of CYPI 1 B2 were found to be no difference between left atria and right atria beth in fibrillation and sinus groups （ all P 〉 0. 05 ）. CVF significantly correlated with left atrial dimension （ r =0. 845, P 〈 0. 001 ）. And aldosterone was found to be significantly positive correlated with left atrial dimension （r = 0. 814, P 〈 0. 001 ） and CVF （r=0. 885, P 〈 0. 001 ）. There was also a positive correlation between the mRNA level of CYP11 B2 and CVF （ R = 0. 757, P 〈 0. 001 ）. Conclusions Atrial structural remodeling during atrial fibrillation is manifested by increased aldosterone level in local atria along with upregulation of the mRNA of CYP11B2. These findings suggest that aldosterone antagonists may be effective in arresting atrial structural remodeling and the development of sustained atrial fibrillation.