抑制天门冬氨酸受体对大鼠急性心肌梗死的影响  

Effect of N-Methyl-D-Aspartate receptor inhibition on acute myocardial infarction in rats

作　　者：温霞[1] 石少波[1] 刘韬[1] 王丹丹[1] 李然[1] 王晞[1] 唐艳红[1] 杨波[1] 黄从新[1] 

机构地区：[1]武汉大学人民医院心内科武汉大学心血管病研究所,武汉430060

出　　处：《中华急诊医学杂志》2015年第9期975-980,共6页Chinese Journal of Emergency Medicine

基　　金：国家重点基础研究发展计划“973项目”（2012CB518604）;湖北省自然科学基金项目（2013CFA117）;中央高校基本科研业务费专项基金（2014302020201）

摘　　要：目的 探讨抑制天门冬氨酸受体（N-Methyl-D-Aspartate receptor,NMDAR）能否减少急性心肌梗死（心梗）后室性心律失常和心梗面积,为急性心梗防治提供实验依据.方法 将45只SD大鼠随机（随机数字法）分为假手术组、心梗组和心梗＋MK801组（NMDAR特异性抑制剂,治疗组）,给药1周后,结扎冠状动脉左前降支制作急性心梗模型;记录心梗后30 min内的室性心律失常,再植入心电图记录器,记录24 h室性心律失常发生的情况;用病理学方法检测缝隙连接蛋白43（connexin43,Cx43）的表达、凋亡小体和心梗面积;用Western blot检测左心室NMDAR的表达量.结果 与假手术组比较,心梗组左心室NMDAR表达量升高（1.12±0.09）vs.（0.54 ±0.06）,P＜0.01.与心梗组比较,治疗组心梗后30 min和24 h室性心律失常发生率显著下降,差异均有统计学意义（P＜0.01）;Cx43分布均匀、表达量较高（1.68±0.27）％v s（0.74±0.15）％,P＜0.01;凋亡小体较少（13.49±3.25）％vs.（32.53±7.21）％,P＜0.01;心梗面积显著下降（36.58±2.57）％vs（43.72 ±3.11）％,P＜0.01;而左心室NMDAR表达量下降（1.12±0.09）vs.（0.81±0.07）,P＜0.01.结论 抑制NMDAR通过上调Cx43表达和抑制凋亡过程,进而减少大鼠急性心梗后室性心律失常和心梗面积.Objective To investigate the effects of N-Methyl-D-Aspartate receptor （NMDAR） inhibition on acute myocardial infarction （AMI） in respect of reduction in the incidence of ventricular arrhythmias （VAs） and infarct size in a rat model in order to provide experimental evidence for the prevention and treatment of AMI.Methods A total of 45 Sprague-Dawley rats were randomly （random number） divided into Sham group,AMI group and AMI plus MK801 （a specific inhibitor of NMDAR） group （treatment group）.The ligation of the left anterior descending coronary artery was performed to induce AMI,and the occurrence of VAs within 30 minutes period during the early stage of infarction was recorded.Then the telemetry ECG was implanted to record the incidence of VAs during the later 24-hour period.The histology staining was performed to measure the level of Cx43,apoptotic body and infarction size;and the expression of NMDAR protein was measured with western-blot.Results Compared with the sham group,the NMDAR expression was markedly increased in the MI group [（1.12 ±0.09） vs.（0.54 ±0.06）,P 〈 0.01];Compared with the MI group,there was marked decrease in the incidences of VAs in treatment group during both 30 min period and 24 hour period （P 〈 0.01）.In addition,the higher Cx43 expression [（1.68±0.27）% vs.（0.74±0.15）%,P〈0.01],fewer apoptotic bodies [（13.49 ±3.25）% vs.（32.53 ± 7.21） %,P 〈 0.01],smaller infarction size [（36.58 ± 2.57） % vs.（43.72 ± 3.11） %,P 〈 0.01] and lower NMDAR expression [（1.12 ±0.09） vs.（0.81 ±0.07）,P 〈0.01] were found in the treatment group than those in MI group.Conclusions The NMDAR inhibition would protect against VAs and reduce infarct size in AMI rats,and the inhibition of Cx43 degradation and apoptosis may be the potential mechanism.

关 键 词：天门冬氨酸受体 急性心肌梗死 室性心律失常 凋亡 

分 类 号：R542.22[医药卫生—心血管疾病]