心房颤动患者心房纤维化分子基础的临床研究  

Clinical on molecular basis of atrial fibrosis in patients with atrial fibrillation investigation

作　　者：柯丹[1] 许春萱[1] 林亚洲[1] 张建成[2] 陈林[1] 林立芳[3] 胡锡衷[1] 

机构地区：[1]福建省心血管病研究所心内科 [2]福建医科大学省立临床学院 [3]福建省心血管病重点实验室

出　　处：《中华心血管病杂志》2005年第5期459-463,共5页Chinese Journal of Cardiology

摘　　要：目的研究风湿性心脏瓣膜病(风心病)心房颤动(房颤)患者心房组织中胶原、基质金属蛋白酶2(matrixmetalloproteinases2,MMP2)及其内源性抑制剂金属蛋白酶组织抑制因子(tissueinhibitorsofmetalloproteinases,TIMPs)的基因转录,探讨房颤患者心房纤维化的分子机制及其在房颤发生、持续中的作用。方法73例风心病接受换瓣手术者分为三组,其中窦性心律组34例,阵发性房颤组9例,持续性房颤组30例。于术中获取右心耳组织,应用半定量逆转录聚合酶链反应(RT PCR)方法,测定心房组织中Ⅰ型胶原、Ⅲ型胶原、MMP2、TIMP1、TIMP2、TIMP3、TIMP4的mRNA水平。结果与窦性心律组比较,Ⅰ型胶原、MMP2的mRNA在阵发性房颤患者(均为P<0.05)、持续性房颤患者(均为P<0.01)心房组织中的表达均明显增加。房颤患者Ⅲ型胶原的mRNA表达虽有增加,但无统计学意义(P>0.05)。持续性房颤组TIMP1、TIMP2、TIMP3的mRNA表达明显下调(均为P<0.01)。TIMP4的mRNA表达水平在各组中差异无统计学意义(P>0.05)。Ⅰ型胶原的mRNA表达水平与左心房内径(r=0.336,P=0.004)、房颤持续时间(r=0.339,P=0.003)呈正相关;MMP2的mRNA表达水平与TIMP2的mRNA表达水平呈负相关(r=-0.326,P=0.006),与Ⅰ型胶原(r=0.322,P=0.006)、左心房内径(r=0.300,P=0.011)。ObjectiveTo determine the molecular mechanisms involved in atrial fibrosis which occurs in patients with atrial fibrillation (AF) and to investigate their effects on the initiation and maintenance of AF.MethodsThe right atrial tissue samples were taken from 73 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients had no history of AF (sinus rhythm group), 9 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA content of collagen type Ⅰ, collagen type Ⅲ, MMP-2, TIMP-1,TIMP-2, TIMP-3 and TIMP-4 was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and normalized to β-actin or GAPDH.Results^Compared to sinus rhythm group, the mRNA of collagen type Ⅰ and MMP-2 increased significantly in the persistent AF group (all, P<0.01), followed by the paroxysmal AF group (all, P<0.05). The mRNA of collagen type Ⅲ was slightly higher in both AF groups than in the sinus rhythm group, but the differences were not statistically significant (P>0.05). The mRNA of TIMP-1, TIMP-2 and TIMP-3 was down-regulated in the persistent AF group (all,P<0.01, respectively), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P>0.05). The mRNA of TIMP-4 remained compatible in each group. The mRNA of collagen type Ⅰ was significantly correlated with left atrial dimension (r=0.336,P=0.004) and AF duration (r=0.339,P=0.003). The mRNA of MMP-2 was significantly correlated with the mRNA of TIMP-2 (r=-0.326,P=0.006), the mRNA of collagen type Ⅰ (r=0.322,P=0.006), left atrial dimension (r=0.300,P=0.011) and AF duration (r=0.300,P=0.010). ConclusionThe increased level of collagen type Ⅰ associated with selective downregulation of TIMP-2 and upregulation of MMP-2 gene expression in atrium could be one of the molecular mechanisms of atrial fibrosis during atrial fibrillation, which correlates with the initiation and maintenance of AF.

关 键 词：心房纤维化 心房颤动患者 逆转录-聚合酶链反应(RT-PCR) 临床研究 分子基础 MMP-2/TIMP-2 金属蛋白酶组织抑制因子 mRNA表达 风湿性心脏瓣膜病 TIMP-1 TIMP-3 房颤持续时间 基质金属蛋白酶 房颤患者 持续性房颤 左心房内径 

分 类 号：R541.7[医药卫生—心血管疾病]