【作者】 汪蓓蕾；

【导师】 徐健；

【作者基本信息】 安徽医科大学 ， 内科学， 2011， 硕士

【摘要】 目的心房颤动(Atrial fibrillation,Af)简称房颤,其发生及维持机制与心房结构重构和电重构有关。心房结构重构促进促进激动各向异性传导,使得心肌细胞间偶联异质性增加,缩短波长的不定向阻滞,有利于折返机制的形成,从而促使房颤的发生及维持;心肌纤维化(myocardial fibrosis,MF)是心房结构重构的主要表现,是心肌细胞外基质(extracellular matrix,ECM)重构的病理实体,基质金属蛋白酶-1 (matrix metalloproteinase-1,MMP-1)及组织型基质金属蛋白酶抑制因子-1(tissue inhibitor of matrix metalloproteinases-1,TIMP-1)共同表达在心肌成纤维母细胞,共同调节胶原代谢,一旦ECM的合成与降解平衡破坏,致使心肌纤维化。本实验通过检测持续性房颤组、阵发性房颤组及窦性心律组三组患者血清中心肌胶原代谢标志物及MMP-1、TIMP-1的表达水平,探讨心肌胶原代谢标志物与不同类型心房颤动的关系,并进一步探讨心肌纤维化对左房内径及左室射血分数的影响。方法选择同期住院的119例患者,其中持续性心房颤动(Persistent atrial fibrilla- tion ,Pe-Af)患者49例,阵发性心房颤动(Paroxysmal atrial fibrillation ,Pa-Af)患者40例,窦性心律(Sinus rhythm, SR)患者30例,分别为Pe-Af组、Pa-Af组、SR组。酶联免疫吸附法测定患者血清中I型胶原羧基端前肽(C-terminal propeptide of collagen type-I ,CICP)、I型前胶原羧基端前肽(C-terminal propeptide of procollagen type I ,PICP)、I型前胶原氨基端前肽(N-terminal propeptide of procollagen type I,PINP)、III型前胶原氨基端肽(N-terminal type III collagen peptide, PIIINP)及基质金属蛋白酶-1(MMP-1)、组织型基质金属蛋白酶抑制因子-1(TIMP-1)的含量,电化学发光免疫法测定患者血清中I型胶原羧基末端交联肽(C-terminal telopeptide of collagen type-I ,ICTP)的表达水平。结果与SR组比较,心房颤动患者血清中CICP、PICP、PIIINP浓度显著增高(P<0.01),且Pe-Af组高于Pa-Af组(P<0.01) ,而3组中PINP无明显差异(P=0.054);与SR组比较,心房颤动患者血清中TIMP-1、ICTP浓度有显著升高(P<0.01),其中与组Pa-Af比较,Pe-Af组MMP-1减低(P<0.01), TIMP-1升高(P<0.01),而ICTP升高不明显(P =0.128)。将CICP、PICP、PIIINP、TIMP-1血清水平分别与左心房(left atrium,LA)内径和左心室射血分数(left ventricular ejection fraction,LVEF)行相关性分析,结果显示CICP、PICP、PIIINP、TIMP-1血清水平与LA内径呈正相关,相关系数分别为r=0.636、r=0.776、r=0.932、r=0.620;与LVEF呈较弱负相关,相关系数分别为r=-0.530、r=-0.568、r=-0.459、r=-0.499。结论(1)不同类型心房颤动患者血清中心肌胶原代谢标志物表达有差异,心肌纤维化可能参与了房颤的发生及维持;(2)MMP-1活化具有时间依赖性,在阵发性房颤组表达增加,但持续性房颤组较窦性心律组无差异;(3)CICP、PICP、PIIINP、TIMP-1血清水平与LA内径大小呈正相关,与LVEF呈线性负相关,表明:左房内径越大,心肌纤维化程度越重;心脏收缩功能越差,心肌纤维化程度越重。更多还原

【Abstract】 Objective Electrical remodeling and structural remodeling has relation to the occurrence and maintenance mechanism of atrial fibrillation. Atrial structural remodeling to promote excitement for anisotropic conduction, making the coupling between the heterogeneity of myocardial cells to increase, shortening the wavelength of the non-directional block is conducive to the formation of reentrant mechanisms, thus contributing to the occurrence and maintenance of atrial fibrillation. Myocardial fibrosis is the main performance of atrial structural remodeling,and the pathologic entity of extracellular matrix remodeling. Collagen is the principal structural protein, and collagen types I and III are the most abundant in the ECM. MMP-1 and TIMP-1 are coexpressed in cardiac fibroblasts and are regulated to maintain the architecture of the ECM,once the balance of synthesis and degradation of ECM damage, resulting in myocardial fibrosis. To investigeted the correlation between circulating levels of myocardial collagen degradation or synthesis markers and the pattern of atrial fibrillation,by detecting serum myocardial collagen metabolism markers and MMP-1, TIMP-1 in Pe-Af group, Pa-Af group and SR group.Methods Serum C-terminal propeptide of collagen type-I (CICP), C-terminal propep- tide of procollagen type I (PICP) ,N-terminal propeptide of procollagen type I (PINP), N-terminal type III collagen peptide(PIIINP), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinases-1 were measured as markers of collagen synthesis and degradation by enzyme-linked immunoadsorbent assay, and C-terminal telopeptide of collagen type-I (ICTP) was assayed using Electrochemiluminescence,in 49 patients with Pe-Af,40 patients with Pa-Af,and 30 healthy control subjects in sinus rhythm.Results CICP, PICP and PIIINP were significantly higher in atrial fibrillation patients than in sinus rhythm study group (P<0.01),and Pe-Af group was higher than Pa-Af group (P <0.01),but no differences were found in PINP levels between atrial fibrillation and sinus rhythm study groups(P=0.054). Atrial fibrillation group had significantly higher levels of TIMP-1 and ICTP(P <0.01) compared with sinus rhythm group.Pe-Af group had lower levels of MMP-1(P <0.01),but higher levels TIMP-1 (P<0.01), when compared with Pa-Af group, and levels of ICTP tended to be higher (P=0.128). In all Af patients taken together, there was a positive correlation between CICP,PICP,PIIINP, and TIMP levels and LA dimension,and the correlation coefficient r were 0.636 ,0.776,0.932,and 0.620 respectively. While there was a weak,inverse correlation between CICP,PICP,PIIINP,and TIMP levels and LVEF,and the correlation coefficient r were -0.530 ,-0.568,-0.459,and -0.499 respectively.Conclusions Serum markers of myocardial collagen metabolism markers differed significantly between persistent atrial fibrillation and paroxysmal atrial fibrillation. Myocardial fibrosis is involved in the presence and maintenance of mechanisms of atrial fibrillation. MMP-1 activation in a time-dependent,which expression increased in the paroxysmal atrial fibrillation group.But no differences were found in MMP-1 levels between atrial fibrillation and sinus rhythm study groups. There was a positive correlation between CICP,PICP,PIIINP, and TIMP levels and LA dimension.While there was a weak,inverse correlation between CICP,PICP,PIIINP,and TIMP-1 levels and LVEF. The LA dimension larger,LVEF lower ,the more obvious of atrial fibrosis.更多还原