短期正中神经刺激对犬快速心房起搏后心房肌电生理和炎症因子的影响  

Effects of short-term median nerve stimulation on atrial electrophysiology and inflammation in canines with rapid atrial pacing

作　　者：张友京 赵庆彦[1] 张淑娟[1] 钱永生[1] 王友成 赵红宜 代子玄[1] 唐艳红[1] 王晞[1] 王腾[1] 黄从新[1] Zhang Youjing;Zhao Qingyan;Zhang Shujuan;Qian Yongsheng;Wang Youcheng;Zhao Hongyi;Dai Zixuan;Tang Yanhong;Wang Xi;Wang Teng;Huang Congxin(Department of Cardiology, Renmin Hospital of Wuhan University,Cardiovascular Research Institute,Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院心血管内科武汉大学心血管病研究所心血管病湖北省重点实验室,430060

出　　处：《中华心律失常学杂志》2018年第6期518-524,共7页Chinese Journal of Cardiac Arrhythmias

基　　金：国家自然科学基金(81670303);湖北省自然科学项目(2014CFB736).

摘　　要：目的探讨短期正中神经刺激(median nerve stimulation,MNS)对犬快速右心房起搏后心房肌电生理特性和炎症反应的影响。方法24只雄性杂种犬武汉大学人民医院实验动物中心提供,按随机数字表法分为对照组(n=4)、假手术组(n=6)、MNS组(n=7)和MNS+甲基牛扁碱(methyllycaconitine,MLA)组(n=7)。其中MLA为α7亚单位的N型乙酰胆碱受体(alpha 7 nicotinic acetylcholine receptor,α7nAChR)拮抗剂。对照组不采取任何干预,假手术组快速右心房起搏3h(800次/min),MNS组MNS联合快速右心房起搏3h,MNS+MLA组于心房及心耳心外膜表面应用MLA(0.5mg)后MNS联合快速右心房起搏3h。假手术组、MNS组和MNS+MLA组于实验基线期和每小时刺激末监测心房有效不应期(AERP)和心房颤动(房颤)诱发情况,取静脉血及心房组织检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和乙酰胆碱(ACh)等水平。对照组取心房组织检测TNF-α、IL-6、ACh表达水平。结果与假手术组和MNS+MLA组相比,MNS组快速刺激3h后犬AERP明显延长(P<0.05),房颤诱发率明显缩短(P<0.05)。假手术组每小时电生理指标变化与MNS+MLA组差异无统计学意义(P>0.05)。快速刺激3h后,与假手术相比,MNS组和MNS+MLA组血清中TNF-α、IL-6等水平均明显降低(P<0.05),ACh显著升高(P<0.05)。快速刺激3h后,与对照组及MNS组比较,假手术组和MNS+MLA组心房组织TNF-α、IL-6浓度明显升高[左心房(LA):假手术组:TNF-α:(0.56±0.09)ng/ml对(0.31±0.05)ng/ml对(0.35±0.07)ng/ml,IL-6:(0.38±0.08)ng/ml对(0.12±0.02)ng/ml对(0.14±0.05)ng/ml,均P<0.05;MNS+MLA组:TNF-α:(0.53±0.11)ng/ml对(0.31±0.05)ng/ml对(0.35±0.07)ng/ml,IL-6:(0.39±0.11)ng/ml对(0.12±0.02)ng/ml对(0.14±0.05)ng/ml,均P<0.05]。与对照组相比,假手术组心肌ACh水平明显减少[LA:(14.0±5.2)ng/ml对(27.0±6.2)ng/ml,P<0.05;右心房(RA):(13.0±5.0)ng/ml对(25.0±6.1)ng/ml,P<0.05],而MNS组及MNS+MLA组ACh水平差异无统计学意义,[MNS组:LA:(24.0±5.8)ng/ml对(27Objective To investigate the effects of short-term median nerve stimulation (MNS) on the atrial electrophysiology and inflammation in canines with rapid atrial pacing. Methods According to the random number table, 24 mongrel dogs were used for the study as follows: control group (n=4), sham-operated group (n=6), MNS group (n=7) and MNS+ MLA (methyllycaconitine) group (n=7). The MLA is alpha 7 nicotinic acetylcholine receptor (α7nAChR) inhibitor.The control group did not take any intervention.The sham-operated group underwent rapid atrial pacing at 800 beats/min for 3 h. MNS Group underwent rapid atrial pacing combined with MNS for 3 h. MNS+ MLA Group underwent rapid atrial pacing combined with MNS and application of MLA (0.5 mg) on the epicardial surface of atrium and atrial appendages for 3 h. The atrial effective refractory period (AERP) and induced atrial fibrillation (AF) at baseline and every hour in the status of non-pacing were measured in dogs undergoing sham-operated group, MNS group and MNS+ MLA group.Then, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), acetylcholine (ACh) in the plasma and atrial tissues were measured.The control dogs were assigned to measure atrial inflammation cytokines. Results Compared with sham-operated group and MNS+ MLA group, the AERP were significantly prolonged (P<0.05), the AF inducibility ratio were significantly increased (P<0.05) in MNS group.There was no significant difference in electrophysiological changes between the sham-operated group and MNS + MLA group.After a 3-hour pacing, the plasma levels of TNF-α and IL-6 were lower (P<0.05), and ACh levels were higher (P<0.05) in MNS group and MNS+ MLA group than sham-operated group.The concentrations of TNF-a and IL-6 in atrial tissues were significantly higher in the sham-operated group and in MNS+ MLA Group than in the control group and MNS Group [LA: sham-operated group: TNF-α: (0.56±0.09) ng/ml vs.(0.31±0.05) ng/ml vs.(0.35±0.07) ng/ml, IL-6: (0.38±0.08) ng/ml vs.(0.12±0.02) ng/ml vs.(0.1

关 键 词：心房颤动 正中神经 胆碱能抗炎通路 炎性因子 

分 类 号：R541.75[医药卫生—心血管疾病]