中国病理生理杂志2025，Vol.41Issue(7)：1334-1344,11.DOI:10.3969/j.issn.1000-4718.2025.07.010
S100A8在阻塞性睡眠呼吸暂停诱发犬心房颤动模型中的作用
Role of S100A8 in atrial fibrillation associated with obstructive sleep ap-nea in dogs
摘要
Abstract
AIM:To investigate the role of S100 calcium-binding protein A8(S100A8)in a canine model of atrial fibrillation(AF)induced by obstructive sleep apnea(OSA).METHODS:Ten adult Beagle dogs were randomly as-signed to OSA(n=5)and control(n=5)groups.The OSA model was established by daily tracheal intubation with alternat-ing airway obstruction and ventilation recovery for 4 h per day,sustained over 12 weeks.Model validation was conducted through arterial blood gas analysis,airway pressure monitoring,and esophageal pressure measurements.Open-chest elec-trophysiological studies were performed to assess atrial effective refractory period(ERP),dispersion of ERP(dERP),and AF inducibility.Tandem mass tag-based quantitative proteomics was used to identify differentially expressed proteins in atrial tissue.Key protein expression and localization were verified using immunohistochemistry and immunofluorescence.RESULTS:Compared with the control group,the OSA group exhibited significantly lower arterial blood pH and partial pressure of oxygen,and higher partial pressure of carbon dioxide in arterial blood,confirming successful model establish-ment.Histopathological analysis revealed disorganized cardiomyocyte architecture,fatty degeneration,inflammatory cell infiltration,and a significant increase in myocardial fibrosis in the OSA group(P<0.05).Electrophysiological data showed increased AF inducibility and dERP,and decreased ERP(P<0.05).Proteomic analysis identified 267 differen-tially expressed proteins,including 128 up-regulated and 139 down-regulated proteins.Immunohistochemical analysis showed significant upregulation of S100A8,S100A9,myeloperoxidase,and nuclear factor-κB p65(P<0.05),while im-munofluorescence demonstrated increased expression of matrix metalloproteinase-9 and transforming growth factor-β1 in the OSA group(P<0.01).CONCLUSION:The OSA promotes upregulation of S100A8 in myocardial tissue,enhances atrial electrical remodeling and fibrosis,and increases susceptibility to AF.These findings suggest that S100A8 may play a key role in the pathogenesis and progression of OSA-related AF.关键词
阻塞性睡眠呼吸暂停/心房颤动/蛋白质组学/纤维化/炎症/S100钙结合蛋白A8Key words
obstructive sleep apnea/atrial fibrillation/proteomics/fibrosis/inflammation/S100 calcium-binding protein A8分类
医药卫生引用本文复制引用
贾索尔·肖克热提,马馨原,王文琦,刘思文,阿迪拉·依米提,雷汭晓,张玲..S100A8在阻塞性睡眠呼吸暂停诱发犬心房颤动模型中的作用[J].中国病理生理杂志,2025,41(7):1334-1344,11.基金项目
国家自然科学基金资助项目(No.82400389) （No.82400389）
新疆维吾尔自治区自然科学基金青年科学基金资助项目(No.2022D01C769) （No.2022D01C769）
国家级大学生创新项目(No.202310760025) （No.202310760025）
新疆维吾尔自治区天山英才培养计划青年托举人才项目(No.2024TSYCQNTJ0048) （No.2024TSYCQNTJ0048）
