摘要
目的探究心脏自主神经节(GP)中电导钙激活钾通道(KCa3.1)介导巨噬细胞极化在心房颤动发生中的作用。方法本研究于2023年在武汉大学心血管病研究所中开展。18只比格犬按随机数字表法分为对照组(n=6)、快速心房起搏(RAP)组(n=6)和TRAM-34组(Kca3.1阻断剂),分别在TRAM-34组和其他组犬的GP中局部注射TRAM-34(0.3 ml,15 mmol/L)和生理盐水。之后,所有组监测右前GP(ARGP)神经活性及心房在体电生理。最终取材后检测ARGP组织中炎性因子水平及巨噬细胞极化情况。结果TRAM-34注射后对非起搏犬心房电生理及ARGP活性无明显影响。RAP明显缩短了心房各部位的有效不应期(ERP),增加了心房颤动易损性和ARGP神经活性,而TRAM-34局部注射有效抑制了这些变化。RAP组和TRAM-34组ARGP组织中CD68+细胞、诱导型一氧化氮合酶(iNOS)、白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α水平均高于对照组。此外,起搏组ARGP组织中CD68+细胞、iNOS和炎性细胞因子水平高于TRAM-34组。结论心房快速起搏时,阻断KCa3.1可抑制GP活性,降低心房颤动易损性,该作用可能与抑制局部巨噬细胞参与GP的炎症反应有关。
Objective To explore the role of conductance calcium activated potassium channel(KCa3.1)in the pathogenesis of atrial fibrillation(AF)by mediating macrophage polarization in cardiac ganglionated plexi(GP).Methods The study was conducted at the Cardiovascular Research Institute of Wuhan University in 2023.Eighteen beagles were randomly divided into the control group(n=6),rapid atrial pacing(RAP)group(n=6)and TRAM-34(a KCa3.1 blocker)group(n=6)according to the random number table method.TRAM-34(0.3 ml,15 mmol/L)and saline were locally injected into GPs in the TRAM-34 group dogs and the other groups,respectively.After that,the neural activity of anterior right GP(ARGP)and atrial electrophysiology were measured.The levels of inflammatory factors and the function of macrophages in ARGP were detected in the three groups then.Results There were no significant effects on atrial electrophysiology and ARGP activity in the non-pacing dogs after injection of TRAM-34.The RAP shortened effective refractory period(ERP)values at all sites and increased the AF vulnerability and ARGP neural activity,while TRAM-34 treatment reversed these changes.The levels of CD68+cells,induced nitric oxide synthase(iNOS),interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-αin ARGP were higher in the RAP group and the TRAM-34 group than those in the control group.Furthermore,the levels of the CD68+cells,iNOS and inflammatory cytokines in ARGP were higher in the RAP group than those in the TRAM-34 group.Conclusions During RAP,blocking KCa3.1 could inhibit the GP activity and reduce the AF vulnerability,which might be related to the reduced inflammatory response in GP mediated by local macrophages.
作者
宋孟洋
鲁志科
张进锋
李鹏飞
马亚哲
赵庆彦
王友成
SONG Meng-yang;LU Zhi-ke;ZHANG Jin-feng;LI Peng-fei;MA Ya-zhe;ZHAO Qing-yan;WANG You-cheng(School of Medicine,Wuhan University of Science and Technology,Wuhan430000,China;Department of Cardiology,Xiaogan Hospital affiliated to Wuhan University of Science and Technology,Wuhan 430000,China;Department of Cardiology,Yunnan First People’s Hospital,Kunming 650100,China;Cardiovascular Research Institute of Wuhan University,Wuhan 430000,China)
出处
《中国心血管病研究》
CAS
2024年第7期642-647,共6页
Chinese Journal of Cardiovascular Research
基金
湖北省自然科学基金(2023AFB409)。
关键词
心房颤动
心脏自主神经节
电导钙激活钾通道
巨噬细胞
炎症
Atrial fibrillation
Ganglionated plexi
Conductance calcium activated potassium channel
Macrophage
Inflammation
