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环状RNA在病态窦房结综合征患者心肌纤维化中的作用研究

The role of circRNA in myocardial fibrosis in patients with sick sinus syndrome
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摘要 目的明确环状RNA在病态窦房结综合征(病窦)患者发病中的作用及其可能机制。方法连续入选南京江宁医院心内科2017年1月至2018年1月收治的经动态心电图诊断病窦的患者40例(病窦组),健康对照组42例,年龄40~80岁。所有患者取空腹静脉血进行心肌纤维化标志物[如转化生长因子β1(TGF-β1)、Ⅰ型前胶原氨基端前肽(PⅠNP)、N末端脑钠肽前体(NT-proBNP)]检测,利用基因芯片技术对两组患者进行环状RNA(hsa_circ_0000186)差异表达分析,筛选上调及下调差异表达基因在所有患者中进行逆转录PCR(RT-PCR)定量验证环状RNA的差异表达,对验证符合的环状RNA进行基因功能(GO)和代谢通路(pathway)分析,并结合心肌纤维化标志物等进行分析。结果与对照组相比,病窦组共有6684个环状RNA表达水平升高,6227个环状RNA表达水平下降。RT-PCR检查显示hsa_circ_0000186/β-肌动蛋白符合芯片检测结果,与对照组相比表达明显降低[(0.003641±0.002221)对(0.005984±0.001833),P<0.05]。TGF-β1(r=-0.418,P<0.05)、PⅠNP(r=-0.264,P<0.05)和NT-proBNP(r=-0.398,P<0.05)水平均与环状RNA定量呈负相关,而P波振幅与环状RNA定量呈正相关(r=0.405,P<0.05)。结论hsa_circ_0000186的降低对心肌纤维化具有预测作用,可以作为病窦的风险评估及未来的干预靶点。 Objective To identify the role and possible mechanism of circRNA in patients with sick sinus syndrome(SSS).Methods We enrolled 82 patients administrated in Jiangning Hospital from January 2017 to January 2018.The patients were divided into two groups according to the dynamic cardiac electrocardiogram(DCG).One group was SSS group(n=40),another was healthy control group(n=42).Some indicators of myocardial fibrosis[transforming growth factorβ1(TGF-β1)、amino-terminal propeptide of type I procollagen(PINP)and N-terminal B-type natriuretic peptide(NT-proBNP)]were detected.Three patient blood samples in each group were examined via RNA sequencing,and the potential functions of circRNA were investigated via bioinformatics analysis.Results A total of 6684 circRNAs were upregulated and 6227 were downregulated in SSS group patients compared to the healthy controls.Hsa_circ_0000186/β-actin was testified coincidence with the array’s results in all the samples,lower than that of healthy controls[(0.003641±0.002221)vs.(0.005984±0.001833),P<0.05].The biomarkers of myocardial fibrosis were elevated in the SSS group.Hsa_circ_0000186 had negtive correlation with the level of TGF-β1(r=-0.418,P<0.05),PINP(r=-0.264,P<0.05)and NT-proBNP(r=-0.398,P<0.05).However,the P wave amplitude was positively correlated with hsa_circ_0000186 quantification(r=0.405,P<0.05).Conclusion The decrease of hsa_circ_0000186 has a predictive effect to the incidence rate of SSS.It may become a new target of the management of SSS.
作者 王君 杨吉猛 张琪 王英 董海翠 方旭 史培青 姜苏蓉 Wang Jun;Yang Jimeng;Zhang Qi;Wang Ying;Dong Haicui;Fang Xu;Shi Peiqing;Jiang Surong(Department of Cardiology,Jiangning Hospital Affiliated to Nanjing Medical University,Nanjing 210020,China;Department of Geriatric Cardiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)
出处 《中华心律失常学杂志》 2021年第3期254-258,共5页 Chinese Journal of Cardiac Arrhythmias
基金 南京市医学科技发展项目(YKK17228)。
关键词 心内膜心肌纤维化症 病态窦房结综合征 环状RNA Endomyocardial fibrosis Sick sinus syndrome CircRNA
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