CAJ | 학술논문

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(0.5 mg/kg)组(MI-VNS-Atr,n=13)和心肌缺血+迷走神经刺激+生胃酮(10 mg/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(0.5 mg/kg)组(M1-VNS-Atr,n=13)和心肌缺血+迷走神经刺激+生胃酮(10 mg/kg)组(MI-VNS-CBX,n=11).心电图监测室性心律失常的发生.Western blot分析Cx43蛋白表达变化.结果结扎冠状动脉30 min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30 min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Cx43表达较成年大鼠明显减少有关.
목적 탐토봉극련접단백43(Cx43)재노년대서심실기중적표체급급성심기결혈시미주신경자격대노년대서결혈성실성심률실상적영향.방법 결찰대서관상동맥전강지제비급성심기결혈모형,수궤분위(1)성년조:가수술조(SO,n=10)、심기결혈조(MI,n=15)、심기결혈+미주신경자격조(MI-VNS,n=15)、심기결혈+미주신경자격+아탁품(0.5 mg/kg)조(MI-VNS-Atr,n=13)화심기결혈+미주신경자격+생위동(10 mg/kg)조(MI-VNS-CBX,n=11).(2)노년조:가수술조(SO,n=10)、심기결혈조(MI,n=15)、심기결혈+미주신경자격조(MI-VNS,n=15)、심기결혈+미주신경자격+아탁품(0.5 mg/kg)조(M1-VNS-Atr,n=13)화심기결혈+미주신경자격+생위동(10 mg/kg)조(MI-VNS-CBX,n=11).심전도감측실성심률실상적발생.Western blot분석Cx43단백표체변화.결과 결찰관상동맥30 min내,노년MI조실성심동과속(실속)화심실전동(실전)발생솔교성년MI조현저증가(P＜0.05);노년MI-VS조실속화실전발생솔여노년MI조상비차이무통계학의의(P＞0.05),단노년MI-VS조불가역성실전발생솔교노년MI조명현감소(P＜0.05).관상동맥결찰30 min후,결혈몰유인기성년조화노년조적총Cx43함량개변(P＜0.05);단결혈인기성년조화노년조적비린산화Cx43함량명현증가,미주신경자격능구명현억제성년조화노년조중결혈인기적Cx43탈린산화(P＜0.05);이아탁품화생위동명현조단료미주신경자격억제결혈인기적Cx43탈린산화적작용(P＜0.05).단실험발현노년SO조Cx43표체교성년SO조명현감소(P＜0.05).결론 노년대서결혈성실성심률실상발생솔명현증가,이미주신경자격적항결혈성실성심률실상적효응명현감약,기궤제가능여노년대서심실기Cx43표체교성년대서명현감소유관.
Objective 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 expression was analyzed by Western blot. Results During the 30 minutes ligation,incidences of ventricular tachycardia (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 nonphosphorylated Cx43 was increased markedly in adult and aged rats compared to that of SO group,respectively.Cx43 dephosphorylation induced by ischemia was significantly suppressed by VNS in adult and aged rats( P ＜0. 05 ). However,the amount of total Cx43 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 incidence 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 ventricle in aged rats.