The correlation between FHF expression in atrial tissue and atrial remodeling in patients with atrial fibrillation
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摘要: 目的 观察心房颤动(AF)患者心房组织成纤维细胞生长因子同源因子(FHF)的表达及其与心房重构的关系。方法 选取因风湿性心脏病在南昌大学第二附属医院心脏大血管外科手术的患者，手术时切取小块右心耳组织，收集临床资料，根据是否合并AF分为窦性心律组(SR组)和心房颤动组(AF组)，实时定量PCR检测各型FHF(FHF1、FHF2、FHF3、FHF4) mRNA表达水平。评估各型FHF mRNA水平与左房内径(LAD)相关性分析，免疫组织化学、Western blot检测两组患者相关FHF表达。结果 共纳入68例病例，其中AF组50例，SR组18例。与SR组相比，AF组B型脑钠肽(BNP)、LAD升高，左室射血分数(LVEF)降低。AF组心房组织FHF1、FHF4的mRNA水平均高于SR组。两组间FHF2、FHF3的mRNA水平无明显差异。FHF1与LAD呈正相关(r=0.477 8，P < 0.05)；FHF2、FHF3、FHF4与LAD无明显相关性。Western Blot和免疫组织化学结果显示AF组心房组织FHF1蛋白表达水平高于SR组。结论 AF患者心房组织中FHF1、FHF4表达升高，FHF1表达与LAD呈正相关，提示FHF1促进心房重构，是AF发生发展的潜在分子靶点。
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关键词:
- 心房颤动 /
- 成纤维细胞生长因子同源因子 /
- 心房重构 /
- 左房内径
Abstract: Objective To investigate the expression of fibroblast growth factor homologous factors(FHF) and its relation with atrial remodeling.Methods We collected the right atrial appendage tissue of patients with rheumatic heart disease undergoing cardiac surgery in the Second Affiliated Hospital of Nanchang University. Patients were divided to group SR(with sinus rhythm) and group AF(with AF history). The expression of FHF mRNA were examined by RT-PCR. The correlation between LAD and FHFs mRNA level were evaluated. The expression of related FHF in atrial tissues were detected by immunohistochemical and Western blot.Results A total of 68 cases were enrolled and 50 cases in the AF group and 18 cases in the SR group. Compared with the SR group, the BNP and LAD in AF group were significantly increased, and the LVEF was significantly decreased. The mRNA expression of FHF1 and FHF4 in AF group were significantly higher than those of SR group. There was no significant difference in FHF2 and FHF3 mRNA levels between the two groups. The expression of FHF1 mRNA was positively correlated with LAD(r=0.477 8, P < 0.05). The expression of FHF2, FHF3, and FHF4 had no correlation with LAD. The expression of FHF1 protein in AF group was higher than that in SR group.Conclusion The expression of atrial FHF1 and FHF4 mRNA in patients with AF were higher than that in patients with SR. And the expression of FHF1 is positively correlated with LAD, suggesting that FHF1 may promote atrial remodeling and be a potential target for the occurrence and development of AF. -
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图 2 FHF1蛋白Western Blot和免疫组织化学结果
Figure 2. Western Blot and immunohistochemical results of FHF1 protein
表 1 引物序列
Table 1. Primer sequence
引物 序列 FHF1 F：5′-GGCGAAATCATCAGATTGGCT-3′ R：5′-ATCCCTGCTGGCTGAATAACC-3′ FHF2 F：5′-GTTACCAAGCTATACAGCCGAC-3′ R：5′-ACAGGGATGAGGTTAAACAGAGT-3′ FHF3 F：5′-CTGTACGCCTCTGCTCTCTAC-3′ R：5′-GCCTTGGTCTTCTTAACTCGGT-3′ FHF4 F：5′-CTTGCCTCCCTCTATCTCCTG-3′ R：5′-CTGAGCTTCCATATGCATCTTTGT-3′ GADPH F：5′-GGAGCGAGATCCCTCCAAAAT-3′ R：5′-GGCTGTTGTCATACTTCTCATGG-3′ 
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表 2 两组患者临床基线资料比较
Table 2. General data
例(%), X±S 项目 SR组(18例) AF组(50例) 男性 6(33.3) 14(28.0) 年龄/岁 55.3±12.6 53.2±11.2 BMI/(kg/m2) 21.5±1.7 21.8±2.9 吸烟史 0 0 酗酒史 0 0 高血压 4(22.2) 6(12.0) 糖尿病 0 1(2.0) 脑卒中 1(5.6) 1(2.0) 甲亢 0 1(2.0) 慢性肾脏病 1(5.6) 1(2.0) 心率/(次/min) 90.3±7.1 89.8±7.2 收缩压/mmHg 116.8±16.2 121.2±13.6 舒张压/mmHg 76.2±12.0 78.6±16.1 BNP/(pg/mL) 100.3±73.5 653.0±752.71) eGFR/(mL/min/1.73 m2) 94.6±40.1 95.2±21.7 血糖/(mmol/L) 4.8±0.7 4.8±0.9 LAD/mm 43.5±6.3 52.0±9.21) LVEF/% 67.7±6.9 50.9±8.11) 与SR组比较，1)P < 0.05。
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