风湿性心脏病心房颤动患者心房组织胶原及转化生长因子β基因表达的研究

Change of gene expression of collagen subtypes and transforming growth factor-beta in human atria during atrial fibrillation

目的 观察风湿性心脏病 (风心病 )心房颤动 (房颤 )患者心房组织中Ⅰ型和Ⅲ型胶原和转化生长因子 β(TGF β1、TGF β2 )基因表达的改变。方法 将 4 9例风心病二尖瓣病变接受换瓣手术者于术中获取的右心耳 (约 10 0mg)分为三组 ,其中窦性心律组 2 0例 ,阵发性房颤组 8例 ,持续性房颤组2 1例 (≥ 6个月 ) ,以 β肌动蛋白为内参照基因 ,通过半定量逆转录 聚合酶链反应 (RT PCR)技术 ,测定各组心房组织中Ⅰ型和Ⅲ型胶原和TGF β1、TGF β2 的mRNA的含量。结果 与风心病窦性心律组相比 ,Ⅰ型胶原、Ⅲ型胶原、TGF β1mRNA表达在阵发性和持续性房颤组均显著增加 ;与阵发性房颤组相比 ,持续性房颤组中这三种基因的表达继续明显增加 ;三组间TGF β2 mRNA表达差异无显著性。结论 风心病患者心房组织中Ⅰ型胶原、Ⅲ型胶原和TGF β1mRNA表达上调可能是心房纤维化发生的分子机制之一 。

Objective The purpose of this study was to determine whether atrial expression of the collagen Ⅰ, collagen Ⅲ and the isoforms of transforming growth factor beta (TGF β) is altered in patients with rheumatic heart disease and atrial fibrillation (AF) Methods A total of 49 patients with rheumatic heart disease were included Twenty patients had no history of AF, 8 patients had paroxysmal AF (pAF) and 21 had chronic persistent AF(≥6 months cAF) Atrial tissue was obtained from the right atrial appendage during valve replacement surgery Total RNA was isolated and reversely transcribed into cDNA In a semi quantitative polymerase chain reaction the cDNA of interest genes and the housekeeping gene β actin were coamplified and separated on an agarose gel by electrophoresis and stained with ethidium bromide The levels of mRNA expression were quantified by densitometry Results The amount of collagen Ⅰ/β actin was increased to 0 91 in pAF group( P =0 001) and to 1 21 in cAF group ( P <0 0001) compared to patients with sinus rhythm (0 58) The expression of collagen Ⅲ /β actin was increased to 0 98 in patients with pAF ( P =0 011) and to 1 24 in those with cAF ( P <0 0001) compared to patients with sinus rhythm (0 69) The expression of TGF β 1 /β actin was increased to 0 46 and to 0 68 in patients with pAF ( P =0 016) and those with cAF ( P <0 0001) respectively compared to patients with sinus rhythm (0 29) Compared with patients with pAF, the gene expression of collagen Ⅰ ( P =0 005), collagen Ⅲ ( P =0 036) and TGF β 1 ( P =0 003) in patients with cAF was also increased The TGF β 2 mRNA content was similar in all groups Conclusion The up regulation of collagen Ⅰ,collagen Ⅲ,TGF β 1 mRNA expression in human atria may have correlation with the initiation or maintenance of AF, and may contribute as a molecular mechanism for the development of atrial fibrosis in patients with rheumatic heart disease, which produces a structural basis for AF