益生菌辅助沙库巴曲缬沙坦联合胺碘酮对心房颤动心肌纤维化的影响机制  

Effect of probiotic-associated sacubactril valsartan combined with amiodarone on myocardial fibrosis in atrial fibrillation

作　　者：毛建云 张明婷 席建芬 韩文杰 李卓琪 赵东坡 裴晓燕 MAO Jianyun;ZHANG Mingting;XI Jianfen;HAN Wenjie;LI Zhuoqi;ZHAO Dongpo;PEI Xiaoyan(Department of Cardiouascular Disease,Zhangjiakou First Hospital,Zhangjiakou 075000,Hebei,China;Second Department of Internal Medicine,Chongli District Hospital,Zhangjiakou 076350,Hebei,China)

机构地区：[1]张家口市第一医院心内科,河北张家口075000 [2]张家口市崇礼区医院内二科,河北张家口076350

出　　处：《中国分子心脏病学杂志》2025年第1期6560-6567,共8页Molecular Cardiology of China

基　　金：河北省医学科学研究课题计划资助(20232068)。

摘　　要：目的 探讨益生菌辅助沙库巴曲缬沙坦联合胺碘酮对心房颤动(AF)心肌纤维化的影响机制。方法 下载基因表达综合数据库(GEO)GSE14975、GSE79768、GSE115574数据集AF患者和窦性心律患者mRNA数据,采用加权基因共表达网络分析(WGCNA)鉴定与AF表型相关的基因模块;采用基因探针富集分析(GSEA)对基因模块中不对称乙酰胆碱酯酶胶原样尾亚基(COLQ)、骨形态发生蛋白2(BMP2)、软骨低聚物基质蛋白(COMP)、血管紧张素Ⅱ1型受体(AGTR1)基因进行功能富集分析;通过STRING网站和Cytoscape软件分析与BMP2相互作用密切的蛋白。选取2021年6月至2022年11月张家口市第一医院收治的接受首次射频消融的AF患者63例(AF组);选取同期窦性心律患者60例作为对照组。根据射频消融术后维持药物的不同,将AF患者分为沙库巴曲缬沙坦联合胺碘酮组(SV+A组)和益生菌辅助沙库巴曲缬沙坦联合胺碘酮组(P+SV+A组)。比较治疗前后SV+A组与P+SV+A组患者临床指标和BMP2、激活素A受体(ACVR2A)、ACVR2B、ACVR1水平的差异。结果 COLQ、BMP2、COMP、AGTR1是AF密切相关的基因,其中BMP2功能富集于转化生长因子β(TGF-β)信号通路。BMP2相互作用密切的蛋白包括BMP2、ACVR2A、ACVR2B、ACVR1,京都基因与基因组百科全书(KEGG)功能富集于TGF-β信号通路、细胞因子与因子受体相互作用;基因本体(GO)功能富集于心腔形态的变化、房室瓣膜形态的发育和变化等。AF组与对照组患者比较,血清BMP2、ACVR2A、ACVR2B、ACVR1水平差异均有统计学意义(P均<0.05)。治疗1年后,与治疗前相比,SV+A组、P+SV+A组患者CHA2DS2-VASc评分、收缩压、舒张压、氨基末端脑利尿钠肽前体、左心房内径、左心室内径、心房容积指数及BMP2、ACVR2A、ACVR2B、ACVR1水平均降低,而左心室射血分数增加(P均<0.05)。相对SV+A组,P+SV+A组心脏结构指标更优,BMP2、ACVR2A、ACVR2B、ACVR1水平更低。结论 益生菌辅助库�Objective To investigate the effect of probiotic-associated sakubatril valsartan combined with amiodarone on myocardial fibrosis in atrial fibrillation(AF). Methods The mRNA data of GSE14975, GSE79768, GSE115574 patients with AF and sinus rhythm were downloaded. Weighted gene co-expression network analysis(WGCNA) was used to identify the gene modules associated with AF phenotype. The function enrichment of collagen-like tail subunit of asymmetric acetylase(COLQ), bone morphogenetic protein 2(BMP2), cartilage oligomeric matrix protein(COMP), angiotensin Ⅱ type 1 receptor(AGTR1) genes in the gene module was analyzed by GSEA. The closely interacting proteins of BMP2 were analyzed by the STRING website and Cytoscape software. Sixty-three patients of AF admitted to the cardiovascular department of Zhangjiakou First Hospital from June 2021 to November 2022, who underwent the first radiofrequency ablation were selected as the research group;Sixty patients with sinus rhythm during the same period were selected as the control group. According to the difference of drugs used after radiofrequency ablation, AF patients were divided into skubactril valsartan combined with amiodarone group( SV + A) and probiotic-associated skubactril valsartan combined withamiodarone group(P + SV + A). Different statistical methods were used to analyze the difference in clinical characteristics and levelsof BMP2, ACVR2A, ACVR2B, ACVR1 between SV + A and P + SV + A groups.Results COLQ,BMP2,COMP,AGTR1weregenes closely related to AF, among which, BMP2 was enriched in transforming growth factor-β( TGF-β) signaling pathway. Theclosely interacting proteins of BMP2 included BMP2, ACVR2A, ACVR2B, ACVR1. TGF-β signaling pathway, cytokine and factorreceptor interaction were enriched by Kyoto encyclopedia of genes and genomes(KEGG) analysis, changes of cardiac cavity morphologyand the development of atrioventricular valve morphology were enriched by gene ontology( GO) analysis. Levels of serum BMP2,ACVR2A, ACVR2B, ACVR1 were different between the re

关 键 词：心房颤动 益生菌 沙库巴曲缬沙坦 骨形态发生蛋白2 转化生长因子Β 

分 类 号：R541.7[医药卫生—心血管疾病]