摘要目的 通过检测老年风湿性心脏病心房颤动(AF)患者心房组织中单核细胞趋化因子-1(MCP-1)的表达水平与核因子κB(NF-κB)的磷酸化水平,探讨MCP 1与NF-κB在AF患者心房纤维化中的作用.方法 26例老年风湿性心脏病患者于换瓣术中获取约200mg的右心房肌组织,分为窦性心律(SR)组12例和AF组14例.Masson染色和纤维化标志物评价心房纤维化,反转录聚合酶链反应技术(RT-PCR)测定细胞因子的mRNA水平,蛋白免疫印迹法(Western blot)测定心房肌组织中MCP-1的蛋白水平和NF-κB的磷酸化水平.结果 AF组与SR组比较,右房心肌组织胶原容积分数增加,分别为(0.42±0.03)与(0.13±0.02),差异有统计学意义(P＜0.05);纤维化标志物转化生长因子-β1、Ⅰ型胶原蛋白和Ⅲ型胶原蛋白、细胞因子白介素-1β、TNF-αmRNA水平增加.MCP-1蛋白表达水平(0.170±0.003)比(0.040±0.005),核因子κB (NF-κB)磷酸化水平(0.35±0.02)比(0.12±0.03),差异有统计学意义(均P＜0.05).细胞因子的表达量、MCP 1的蛋白表达水平及NF-κB的磷酸化水平均与右房心肌组织胶原容积分数呈正相关.结论 风湿性心脏病AF患者心肌组织中NF-κB的激活可能诱导MCP-1的表达增加,继而刺激细胞因子的分泌,引起细胞外基质沉积促进心房纤维化、从而参与AF的发生与维持.

abstractsObjective To explore the relationship of the expression level of monocyte Chemotactic protein-1 and nuclear factor κB(NF κB)with atrial fibrosis of atrial fibrillation patients with rheumatic heart disease.Methods About 200 mg right atrial tissue were taken from 26 patients with rheumatic heart disease undergoing valve replacement surgery and divided into sinus rhythm (SR) group (n=12) and atrial fibrillation (AF) group (n=14).Masson staining and atrial myocardial fibrosis markers were used to determine the level of fibrosis.The mRNA levels of cytokines in atrial tissue were measured by reverse transcription polymerase chain reaction (RT-PCR)The protein level of MCP-1 and phosphorylation of NFκB in atrial tissue were detected by Western blotting.Results Compared with SR group,the AF group showed that collagen volume fraction (AF:0.42 ± 0.03;SR:0.13 ± 0.02),the mRNA levels of myocardial fibrosis markers such as transforming growth factor (TGF)-β1,type Ⅰ collagen and type Ⅲ collagen,and cytokines such as IL-1β and TNF-α,and the protein level of MCP-1 (AF:0.170±0.003;SR:0.040±0.005) and level of phosphorylation of NF-κB (AF:0.35 ± 0.02;SR:0.12 ± 0.03) were significantly increased (all P＜0.05).In addition,the expression levels of cytokines,the protein expression level of MCP1 and the phosphorylation level of NF-κB were positively correlated with collagen volume fraction of the right atrial myocardial tissue (all P＜0.05).Conclusions Activation of NF-κB may induce the expression of MCP-1 in the myocardial tissue of patients with rheumatic heart disease,and sequentially stimulate the secretion of cytokines and extracellular matrix deposition,and finally participate in the occurrence and persistence of atrial fibrillation.