脑-星状神经节-心房通路调控巨噬细胞对犬急性脑卒中后心房颤动的影响

Effects of brain-stellate ganglion-atrium pathway regulating macrophages on atrial fibrillation vulnerability after acute stroke in dogs

目的探讨脑-星状神经节-心房通路对犬急性脑卒中(AS)后心房颤动(房颤)的影响及其调控机制。方法26只比格犬按随机数字表法随机分为假手术组(Sham组,n=6)、急性脑卒中组(AS组,n=7)、星状神经节消融(stellate ganglion ablation)组(SGA组,n=6)和巨噬细胞清除组(CL组,n=7)。Sham组犬开颅手术后不行大脑中动脉阻塞(middle cerebral artery occlusion,MCAO);AS组行MCAO后建立AS模型;SGA组行MCAO后行左侧星状神经节(LSG)消融;CL组行MCAO后于左、右心房注射磷酸二钠脂质体。4组犬于3 d后记录心房有效不应期(ERP)、有效不应期离散度(dERP)、房颤诱发率、交感神经活性、巨噬细胞及相关炎性细胞因子表达水平。结果与Sham组比,AS组心房dERP[(14.8±2.1)ms对(36.5±4.8)ms,P<0.05]和房颤诱发率[(4.4±2.2)%对(24.4±4.4)%,P<0.05]均明显升高,而SGA组与CL组dERP[(36.5±4.8)ms对(21.0±3.6)ms,(17.6±2.8)ms,均P<0.05]和房颤诱发率[(24.4±4.4)%对(5.5±2.7)%,(5.3±3.2)%,均P<0.05]均较AS组显著降低;Sham组、SGA组和CL组间房颤诱发率和巨噬细胞水平差异无统计学意义;AS组和CL组LSG活性均较Sham和SGA组明显增加;AS组巨噬细胞和相关炎性因子浸润明显高于Sham、CL和SGA组。结论脑-星状神经节-心房系统可通过增加心房组织巨噬细胞水平增加AS模型犬房颤的易患性。

Objective The aim of this study was to investigate the effects of the brain-stellate ganglion-atrium pathway on atrial fibrillation(AF)vulnerability after acute stroke in dogs.Methods Twenty-six beagle dogs were randomly divided into sham group(Sham,n=6),acute stroke group(AS,n=7),stellate ganglion ablation group(SGA,n=6)and clodronate liposomes group(CL,n=7).In the Sham group,the dogs received craniotomy without right middle cerebral artery occlusion(MCAO).The dogs in the AS group underwent MCAO.In the SGA group dogs after underwent MCAO,the left stellate ganglion(LSG)was ablated.CL group dogs underwent MCAO,and disodium phosphate monophosphate was injected into the left and right atrium sequentially.Three days later,atrial electrophysiology and neural activity and the expression levels of macrophages and related inflammatory factors in the atrium were studied in all of the dogs.Results Compared with the Sham group dogs,the AS dogs had a higher dispersion of the effective refractory period(dERP)and AF inducibility[dERP:(14.8±2.1)ms vs.(36.5±4.8)ms,P<0.05;AF inducibility:(4.4±2.2)%vs.(24.4±4.4)%,P<0.05].However,SGA or CL injection sharply suppressed the increased dERP and AF inducibility[dERP:(36.5±4.8)ms vs.(21.0±3.6)ms,(17.6±2.8)ms,P<0.05;AF inducibility:(24.4±4.4)%vs.(5.5±2.7)%,(5.3±3.2)%,P<0.05].There was no significant difference in AF inducibility and macrophage infiltration in the atrium among the Sham group,the SGA group and the CL group.The infiltration of macrophages and related inflammatory factors in the AS group was significantly higher than in the Sham group,the SGA group and the CL group.Conclusion A brain-stellate ganglion-atrium pathway may increase AF vulnerability after acute stroke through macrophage activation.