慢性心房颤动患者心房肌盐皮质激素受体和11βHSD2表达研究

Expression of mineralocorticoid receptor and ll-beta-hydroxysteroid dehydrogenase type 2 in human atria during chronic atrial fibrillation:study of 25 cases

目的探讨心房颤动患者心房肌组织盐皮质激素受体(MR)和赋予 MR 特异性的关键酶11β-羟基类固醇脱氢酶Ⅱ(11βHSD2)的 mRNA 和蛋白表达改变。方法入选进行人工心脏瓣膜置换术的风湿性心脏病患者25例,其中窦性心律12例,慢性心房颤动(心房颤动时程≥6月)13例。术前进行经胸超声心动图检查,所有患者在术前均签订知情同意书,于手术时取左右心房侧壁组织。用实时荧光定量 PCR 检测 MR 和11βHSD2的 mRNA 水平,Western 印迹检测 MR 和11βHSD2的蛋白表达改变。结果心房颤动组比窦性心律组左房内径显著扩大(P<0.01);房颤组患者 MR mRNA表达(右房:5.37±1.15 vs 2.67±1.09,左房:5.19±1.14 vs 2.70±0.82 P 均<0.01)和11βHSD2mRNA 表达(右房:0.86±0.14 vs 0.33±0.12,左房:0.95±0.15 vs 0.37±0.10 P 均<0.01)均明显增加;同时房颤组患者 MR 和11βHSD2蛋白表达也较窦性心律者明显增加,MR 分别为右房:1.65±0.72 vs 0.86±0.33(P<0.01);左房:1.72±0.62 vs 0.97±0.37(P<0.05)。11βHSD2分别为右房:-1.18±0.64 vs 0.71+0.21(P<0.01);左房:1.36±0.58 vs 0.85±0.15(P<0.05);但在左右心房之间无论是在窦性心律或心房颤动时,MR 和11βHSD2二者在 mRNA 水平和蛋白表达水平差异均无统计学意义(P>0.05)。结论心房颤动时心房肌组织 MR 和11βHSD2表达增加,醛固酮受体拮抗剂将可能对心房颤动发挥治疗作用。

Objective To investigate the mRNA and protein expression of mineralocorticoid receptor （MR） and 11-beta-hydroxystemid dehydrogenase type 2 （11βHSD2 ）, which plays a crucial role in the human heart to confer specificity on MR, in patients with chronic atrial fibrillation. Methods Twentyfive patients of rheumatic heart valve disease, 12 with sinus rhythm, and 13 with chronic atrial fibrillation for 6 months or over, underwent trausthoracic echocardiogruphy and mitral/aortic valve replacement operation during which right atrial lateral wall tissue samples were obtained and left atrial lateral wall tissue samples were obtained from 14 of them in addition. Reahime quantitative PCR was used to determine the mRNA expression of MR and 11βHSD2 and Western blotting was employed to detect the protein expression of MR and 11βHSD2 in the atrial myocardnim. Results The left atrial diameters increased markedly in the atrial fibrillation group as compared to the sinus rhythm group（P 〈0.01 ）. The mRNA expression of MR in the right atrium of the patients with atrial fibrillation was 5.37 ± 1. 15, significantly higher than that of the patients with sinus rhythm （2.67 ± 1.09, P 〈0.01 ）, the mRNA expression of MR in the left atrium of the patients with atrial fibrillation was 5.19 ± 1.14, significantly higher than that of the patients with sinus rhythm （270 ± 0. 82, P 〈 0.01 ）. The mRNA expression of 11βHSD2 in the right atrium of the patients with atrial fibrillation was 0. 86 ± 0. 14, significantly higher than that of the patients with sinus rhythra （0. 33 ± 0.12, P〈0.01）, and the mRNA expression of 11βHSD2 in the left atrium of the patients with atrial fibrillation was 0.95±0. 15, significantly higher than that of the patients with sinus rhythm （0.37±0. 10, P〈0.01 ）. The protein expression of MR in the right atrial tissue of the patients with atrial fibrillation was 1.65±0.72, significantly higher than that of the patients with sinus rhythra （0.86±0.33, P〈0.01 ） ; and the protein expression d MR in the left atrial tissue of the patients with atrial fibrillation was 1.72±0.62, significantly higher than that of the patients with sinus rhythra （0.97± 0. 37a, P 〈 0. 05 ）. The proteinexpression of 11βHSD2 in the right atrial tissue of the patients with atrial fibrillation was 1.18± 0.64, significantly higher than that of the patients with sinus rhythm （0.71±0. 21, P 〈0.05） ; and the protein expression of 11βHSD2 in the left atrial tissue of the patients with atrial fibrillation was 1.36 ± 0.58, significantly higher than that of the patients with sinus rhythm （ 0. 85 ± 0. 15, P 〈 0.05 ）. The mRNA expression and protein expression of MR and 11βHSD2 were not significantly different between the left atria and right atria beth in the fibrillation and sinus groups （ all P 〉 0.05）. Conclusion The mRNA expression and protein expression of MR and 11βHSD2 are upregulated in atrial fibrillation and aldosterone antagonists may be effective to arrest the development of sustained atrial fibrillation.