心房颤动患者衰老基因的表达及其与心肌纤维化的相关性

Study of the expression of KLOTHO gene and its correlation to myocardial fibrosis in the atrial tissues with atrial fibrillation

目的探讨心房颤动(简称房颤)患者KLOTHO基因的表达及其与纤维化的相关性。方法 60例行心脏手术患者按心脏节律分为窦性心律组、阵发性房颤组及持续性房颤动,每组20例。采用用实时荧光定量聚合酶链式反应的方法研究KLOTHO基因mRNA在患者心房肌组织中的表达,及其与血清中心肌纤维化指标Ⅰ型前胶原羧基端肽(PⅠCP)、Ⅲ型前胶原氨基端肽(PⅢNP)的关系。并行心肌组织切片HE染色来观察心肌纤维化的程度。结果①与窦性心律组相比,房颤组左房明显扩大(P<0.05),持续性房颤组的左房内径大于阵发性房颤组(P<0.05)。②与窦性心律组相比,阵发性房颤、持续性房颤组心房组织的KLOTHO mRNA水平均明显减少(P<0.05);持续性房颤组KLOTHO mRNA表达较阵发性房颤组亦明显减少(P<0.01)。③窦性心律组心肌间质中仅见极少量胶原纤维;阵发性房颤组心肌间质中胶原沉积增多,心肌肌束周围可见明显胶原纤维包绕;持续性房颤组心肌间质中纤维组织显著增生,心肌肌束被大量的条索状胶原纤维所分隔。④与窦性心律组相比,房颤组血清PⅠCP、PⅢNP含量明显增高(P<0.01),且持续性房颤组PⅠCP、PⅢNP含量较阵发性房颤组明显增加(P<0.05);⑤房颤患者心肌KLOTHO mRNA水平与左房内径、血清中PⅠCP、PⅢNP呈独立的、显著的负相关关系(P<0.01)。结论房颤患者KLOTHO基因的表达增加,心肌纤维化的程度减少,提示KLOTHO基因可能与心房纤维化有关。

Objective Investigate KLOTHO gene expression in patients with atrial fibrillation（AF） and its correlation with fibrosis. Methods Sixty patients undergone cardiac surgery were divided into three groups according to the heart rhythm：sinus rhythm group,persistent AF and paraxysmal AF group. Each group has 20 patients. The mRNA amounts of Klotho gene were studied by real time quantitative polymerase chain reaction（RT-PCR） method with the right atrial tissues of AF. And to study the correlation to P I CP,PIII NP in serum, which are myocardial fibrosis signal . Myocardial tissue HE staining to observe the extent of myocardial fibrosis. Results ①Left atrial diameter were significantly increased in patients with AF（P〈0.05）. Which persistent AF group higher than paroxysmal AF group （ P 〈 0. 05 ） ;② The mRNA level of KLOTHO significantly decreased in both paroxysmal AF and persistent AF groups compared with the sinus rhythm group（P〈0. 05; P〈0.05） and the persistent AF group was lower than paroxysmal AF groups （P〈 0.01） ;③There was very few collagen fiber in myocardial stroma in sinus rhythm group; Myocardial stroma collagen deposition multiplied in paroxysmal AF group, apparent collagen fiber around cardiac muscle bundle;Myocardial stroma fibrous tissue remarkable hyperplasia in persistent AF group,and cardiac muscle bundle was spaced by the amount of the bands of collagen fiber;④Compared with the sinus rhythm group, the significant increase was observed in the persistent AF compared with paroxysmal AF groups in the concentrations of serum P I CP, PIII NP （P〈0.01） and the persistent AF group was higher than paroxysmal AF groups（P〈0.05） ;⑤There was a conspicuous and independent negative correlation between the expression of KLOTHO mRNA and the P I CP, Pm NP and left atrial diameter（P〈0.01）. Conclusions The KLOTHO gene m-RNA level is decreased in AF, and the degree of myocardial fibrosis is increased, it,indicates the KLOTHO gene may be involved in atrial remodeling.