缝隙连接蛋白43在老年大鼠缺血性室性心律失常中的作用  

Effects of Connexin 43 expression on ischemia-induced ventricular arrhythmias in aged rats

作　　者：胡笑容[1] 周晓亚[1] 徐昌武[1] 崔博[1] 温华知[1] 鲁志兵[1] 江洪[1] 

机构地区：[1]武汉大学人民医院心内科,430060

出　　处：《中华心律失常学杂志》2010年第3期219-223,共5页Chinese Journal of Cardiac Arrhythmias

摘　　要：目的探讨缝隙连接蛋白43（Cx43）在老年大鼠心室肌中的表达及急性心肌缺血时迷走神经刺激对老年大鼠缺血性室性心律失常的影响。方法结扎大鼠冠状动脉前降支制备急性心肌缺血模型，随机分为（1）成年组：假手术组（SO，n：10）、心肌缺血组（MI，n=15）、心肌缺血＋迷走神经刺激组（MI—VNS，n=15）、心肌缺血＋迷走神经刺激＋阿托品（0．5mg／kg）组（MI—VNS—Atr，n=13）和心肌缺血＋迷走神经刺激＋生胃酮（10mg／kg）组（MI—VNS—CBX，n=11）。（2）老年组：假手术组（SO，n=10）、心肌缺血组（MI，n=15）、心肌缺血＋迷走神经刺激组（MI—VNS，n=15）、心肌缺血＋迷走神经刺激＋阿托品（0．5mg／kg）组（MI—VNS．Atr，n=13）和心肌缺血＋迷走神经刺激＋生胃酮（10mg／kg）组（MI—VNS—CBX，n=11）。心电图监测室性心律失常的发生。Westernblot分析Cx43蛋白表达变化。结果结扎冠状动脉30min内，老年MI组室性心动过速（室速）和心室颤动（室颤）发生率较成年MI组显著增加（P〈0．05）；老年MI—VS组室速和室颤发生率与老年MI组相比差异无统计学意义（P〉0．05），但老年MI—VS组不可逆性室颤发生率较老年MI组明显减少（P〈0．05）。冠状动脉结扎30min后，缺血没有引起成年组和老年组的总Cx43含量改变（P〈0．05）；但缺血引起成年组和老年组的非磷酸化Cx43含量明显增加，迷走神经刺激能够明显抑制成年组和老年组中缺血引起的Cx43脱磷酸化（P〈0．05）；而阿托品和生胃酮明显阻断了迷走神经刺激抑制缺血引起的Cx43脱磷酸化的作用（P〈0．05）。但实验发现老年SO组Cx43表达较成年SO组明显减少（P〈0．05）。结论老年大鼠缺血性室性心律失常发生率明显增加，而迷走神经刺激的抗缺血性室性心律失常的效应明显减弱，其机制可能与老年大鼠心室肌Cx43Objective To investigate the expression of connexin43 （ Cx43 ） and effect of vagal nerve stimulation （VNS） on ventricular tachyarrhythmias during acute myocardial ischemia（MI） in aged rats. Methods Male Sprague-Dawley rats [ Adult group （ ≤4 months） and Aged group （ ≥24 months） ） ：MI （n = 15 ） ： ligated left anterior descending coronary for 30 minutes; MI-vagal nerve stimulation（VNS） （n = 15 ） ; MI-VNS- atropine （0.5 mg/kg, n = 13 ） ; MI-VNS-carbenoxolone （ 10 mg/kg, n = 11 ） ; sham operation （ SO, n = 10 ） ： without coronary ligation. Ventricular arrhythmias were monitored by an electrocardiogram. Cx43 protein expres- sion was analyzed by Western blot. Results During the 30 minutes ligation, incidences of ventricular tachycar- dia （VT） and ventricular fibrillation（VF） in aged rats increased significantly compared to those of adult rats （ P 〈 0. 05 ）. VNS did not affect the occurrence of VT and VF （ both P 〉 0.05 ） ; however, VNS suppressed the occurrence of irreversible VF （P 〈 0.05 ）; both atropine and carbenoxolone （a gap junction inhibitor） could abolish the effect of VNS on ischemia-induced irreversible VF （ both P 〈0. 05 ）. Ischemia did not result in changes of total Cx43 amount in adult and aged rats compared to that of SO group, respectively. The amount of non- phosphorylated Cx43 was increased markedly in adult and aged rats compared to that of SO group, respectively.Cxd3 dephosphorylation induced by ischemia was significantly suppressed by VNS in adult and aged rats （ P 〈 0.05）. However,the amount of total Cxg3 of SO group in aged rats was significantly decreased by 50% compared to that of SO group in adult rats （P 〈 0. 05 ）. Conclusion The present study suggested that the inci- dence of ischemia-induced ventricular tachyarrhythmias increased markedly and the anti-arrhythmic effect of VNS was decreased significantly in aged rats,which may be associated with reduction of Cx43 protein of ventri- cle in

关 键 词：缝隙连接蛋白43 室性心律失常 心肌缺血 迷走神经 老年 

分 类 号：R541.7[医药卫生—心血管疾病]