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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 To investigate the expression of KLOTHO gene in patients with atrial fibrillation (AF) and its correlation with fibrosis. Methods Sixty patients undergoing cardiac surgery were divided into sinus rhythm group, paroxysmal atrial fibrillation group and persistent atrial fibrillation according to cardiac rhythm, with 20 cases in each group. To investigate the expression of KLOTHO mRNA in atrial myocardium by real-time fluorescent quantitative polymerase chain reaction (PCR-RFLP), and to investigate the relationship between KLOTHO mRNA expression and myocardial fibrosis indicators such as PⅠCP, Peptide (PⅢNP) relationship. Parallel myocardial tissue sections HE staining to observe the degree of myocardial fibrosis. Results ① Compared with sinus rhythm group, left atrium of atrial fibrillation group was significantly enlarged (P <0.05), left atrial diameter of persistent atrial fibrillation group was higher than that of paroxysmal atrial fibrillation group (P <0.05). Compared with sinus rhythm group, KLOTHO mRNA in atrial fibrillation group and persistent atrial fibrillation group were significantly decreased (P <0.05); KLOTHO mRNA expression in persistent atrial fibrillation group was higher than that in paroxysmal atrial fibrillation group Also significantly reduced (P <0.01). (3) Only a very small amount of collagen fibers were found in the myocardial interstitium of sinus rhythm group. Collagen deposition in myocardial interstitium increased in paroxysmal atrial fibrillation group, and obvious collagen fibers surrounded the muscle bundle of myocardium. The myocardial interstitial fibers Significant proliferation of tissue, myocardial muscle bundle is separated by a large number of cord-like collagen fibers. Compared with sinus rhythm group, the contents of PⅠCP and PⅢNP in atrial fibrillation group were significantly increased (P <0.01), and the levels of P Ⅰ CP and P Ⅲ NP in persistent atrial fibrillation group were significantly higher than those in patients with atrial fibrillation (P <0.05). ⑤ The KLOTHO mRNA level in myocardium of AF patients was independent and significant negative correlation (P <0.01) with left atrial diameter, PⅠCP and PⅢNP in serum. Conclusion The expression of KLOTHO gene is increased in patients with atrial fibrillation, and the degree of myocardial fibrosis is decreased, suggesting that KLOTHO may be associated with atrial fibrosis.