抑制MAPK14通过减轻线粒体自噬改善AngⅡ诱导的心房颤动  

Inhibition of MAPK14 Improves AngⅡ-Induced Atrial Fibrillation by Reducing Mitophagy

作　　者：王璐[1] 桑婉玥 简易 韩亚凡 王菲菲 李耀东[1] WANG Lu;SANG Wanyue;JIAN Yi;HAN Yafan;WANG Feifei;LI Yaodong(Department of Pacing and Electrophysiology,Xinjiang Key Laboratory of Cardiac Electrophysiology and Remodeling,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,Xinjiang,China;Shandong First Medical University Affiliated Provincial Hospital,Jinan 250117,Shandong,China)

机构地区：[1]新疆医科大学第一附属医院心脏中心起搏电生理科,新疆心电生理与心脏重塑重点实验室,新疆乌鲁木齐830054 [2]山东第一医科大学附属省立医院,山东济南250117

出　　处：《心血管病学进展》2024年第4期373-378,共6页Advances in Cardiovascular Diseases

基　　金：新疆维吾尔自治区杰出青年科学基金(2022D01E22);新疆维吾尔自治区研究生创新项目(XJ2023G167,XJ2023G155)。

摘　　要：目的探讨丝裂原激活蛋白激酶14(MAPK14)在血管紧张素Ⅱ(AngⅡ)诱导的大鼠心房颤动(AF)中的作用及潜在机制。方法构建AngⅡ诱导的大鼠AF易感模型,使用SB203580抑制MAPK14的表达,采用彩色超声显像仪器评估左心房内径和左室射血分数等;电生理仪检测心房有效不应期、AF诱发率及AF平均持续时间等电生理指标;透射电镜观察线粒体结构;Masson染色检测左心房纤维化程度;免疫组织化学染色检测微管相关蛋白1轻链3表达;Western blot检测MAPK14、p-MAPK14和线粒体自噬标志parkin及P62的表达水平。结果与对照组相比,AngⅡ组大鼠心房组织中MAPK14和p-MAPK14表达上调(P均<0.005)。与AngⅡ组相比,抑制MAPK14能够改善AF诱发率及AF持续时间(P均<0.0005),并减轻大鼠心房组织的线粒体自噬(P均<0.05),且显著改善心脏和线粒体结构受损(P均<0.05)。结论抑制MAPK14可通过减轻线粒体自噬改善AngⅡ诱导的大鼠AF。Objective To explore the role and potential mechanism of mitogen-activation protein kinase 14(MAPK14)in angiotensinⅡ(AngⅡ)-induced atrial fibrillation(AF)in rats.Methods To establish a rat model of AF susceptibility induced by AngⅡ,SB203580 was used to inhibit the expression of MAPK14.The left atrial dimension and left ventricular ejection fraction were evaluated by color Doppler ultrasound.Electrophysiological indexes such as atrial effective refractory period,AF induction rate and average duration of AF were measured by electrophysiological instrument.The structure of mitochondria was observed by transmission electron microscope.The degree of left atrial fibrosis was detected by Masson staining.The expression of LC3 was detected by immunohistochemical staining.The expression levels of MAPK14,p-MAPK14,mitophagy markers parkin and P62 were detected by Western blot.Results Compared with the control group,the expression of MAPK14 and p-MAPK14 in atrial tissue of AF rats was up-regulated in AngⅡgroup(P<0.005).Compared with AngⅡgroup,inhibition of MAPK14 could improve the induction rate of AF and the duration of AF(P<0.0005),reduce mitophagy in rat atrium(P<0.05),and significantly improve the structural damage of heart and mitochondrial(P<0.05).Conclusion Inhibition of MAPK14 could improve AngⅡ-induced AF of rats by reducing mitophagy.

关 键 词：心房颤动 线粒体自噬 丝裂原激活蛋白激酶14 血管紧张素Ⅱ 

分 类 号：R541.75[医药卫生—心血管疾病]