【摘要】 目的观察右美托咪定对离体家兔心缺血-再灌注（ischemia-reperfusion,IR）损伤后心肌复极不均一性及Cx43表达的影响,探讨Cx43在右美托咪定抑制IR损伤心肌复极不均一性中的作用。方法健康成年家兔18只,体重（2.0±0.5）kg,成功制备Langendorff离体心脏灌注模型,KH液平衡灌流15min后随机均分为三组,每组6只。空白对照组（C组）:持续平衡灌注37℃K-H液150min;IR组:K-H液继续灌流15 min后停灌,注射4℃Thomas液10 ml/kg使心脏停搏60min,心脏周围用4℃Thomas液保护,30min半量复灌4℃Thomas液5ml/kg,60min时复灌K-H液;右美托咪定组（DEX组）:于K-H液及Thomas液中加入右美托咪定25ng/ml,余同IR组。记录平衡灌流15min（T₀）、继续灌流15min（平衡30min,T₁）、复灌30min（平衡120min,T₂）、复灌60min（平衡150min,T₃）的HR及三层心肌（内膜、中膜、外膜）90%单相动作电位时程（MAPD90）并以此计算跨室壁复极离散度（transmural dispersion of repolarization,TDR）,观察心脏复灌时心律失常发生情况、复跳时间,T₃时取左心室组织采用Western blot法、免疫组化法检测左室心肌组织Cx43的表达及分布。结果 DEX组复跳时间明显短于IR组（P<0.05）;与T₀时比较,T₂、T₃时IR组、DEX组HR明显减慢,TDR明显增大（P<0.05）;与IR组比较,T₁^T₃时DEX组HR明显减慢,T₂、T₃时DEX组TDR明显减小（P<0.05）。与C组比较,IR组、DEX组Cx43表达明显减少（P<0.05）且分布不均,且DEX组明显多于IR组（P<0.05）。结论右美托咪定抑制IR损伤后心肌复极不均一性,从而起到稳定IR损伤心肌心电传导,降低复灌性心律失常发生率的作用,其机制可能与右美托咪定抑制缝隙连接失偶联、抑制Cx43表达减少及分布紊乱有关。更多还原

【Abstract】 Objective To investigate the effect of dexmedetomidine on myocardial repolarization heterogeneity and the expression of Cx43 during ischemia-reperfusion and the role of Cx43 in the dexmedetomidine for inhibition of myocardial repolarization heterogeneity during ischemia-reperfusion in isolated rabbit hearts.Methods Eighteen healthy adult rabbits,weighing（2.0±0.5）kg,were randomly divided into three groups after Langendorff isolated heart perfusion model had been prepared and K-H fluid had been perfused and balanced 15 min.In the control group（group C）,37℃ K-H fluid was continuously perfused and balanced for 150 min.In group IR,K-H fluid was stopped after perfusion continue filling for 15 min,and then made the cardiac stop for 60 min with the injection of Thomas solution 10ml/kg while the heart was protected by the 4℃ Thomas solution around.Following the reperfusion of 4℃ Thomas solution 5ml/kg was performed for 30 min and the heart was resuscitated by the perfusion of K-H fluid for 60 min.In dexmedetomidine group given（group DEX）,dexmedetomidine was added in the K-H fluid and the Thomas solution 25ng/ml.The other procedures were the same as those of group IR.The heart rate（HR）,90%monophasic action potential duration（MAPD90）were recorded at the time of balance perfusion record15min（T₀）,continue perfusion 15min/balance 30 min（T₁）,reperfusion 30 min/balance 120 min（T₂）and reperfusion 60min/balance 150 min（T₃）.The transmural dispersion of repolarization（TDR）was calculated.To observe the cardiac reperfusion arrhythmia and rebeating time and recording.Detection expression of Cx43 in the left ventricular myocardial by Western blot and immunohistochemistry at T₃.Results Group DEX cardiac resuscitation time was significantly shorter than that of group IR（P<0.05）.In group DEX.Compared with T₀,HR was significantly decreased and TDR was significantly increased in groups IR and DEX at T₂、T₃（P<0.05）.Compared with group IR,the TDR of group DEX was significantly decreased at T₂、T₃（P<0.05）.Compared with group C,the expression of Cx43 was decreased（P<0.05）and the distribution was not uniform in groups IR and DEX.Compared with group IR,the expression of Cx43 was decreased（P <0.05）and the distribution was improved in group DEX.Conclusion Dexmedetomidine could inhibits myocardial repolarization heterogeneity of ischemia-reperfusion injury,and thus play a stable cardiac conduction,reduce reperfusion arrhythmias,and its mechanism may be that dexmedetomidine could inhibits gap junctional uncoupling and inhibits expression and distribution of connexins decreased.更多还原