右美托咪定预处理对大鼠缺血再灌注心律失常的影响及机制研究

Efects and mechanisms of dexmedetomidine preconditioning on ischemia-reperfusion arrhythmia in rats

目的观察右美托咪定预处理对大鼠缺血再灌注心律失常的影响及机制。方法 2015年3-6月于武汉大学基础医学院选择30只雄性SD大鼠,随机分为假手术组(SO组)、缺血再灌注组(I/R组)、右美托咪定预处理组(DEX组)各10只。I/R组、DEX大鼠先结扎冠状动脉30 min引起心肌缺血,再松开结扎线给予心肌再灌注120min。SO组只带线不结扎,DEX组在缺血前2 h给予右美托咪定100μg/kg腹腔注射,I/R组给予等体积生理盐水。监测记录各组缺血再灌注心律失常的发生情况,以实时定量PCR法检测心肌组织L型钙通道(Cav1.2)、钠钙交换体(NCX)mRNA的水平。结果 SO组心律无明显变化,心律失常评分为0分。DEX组心律失常发生率低于I/R组,缺血30 min和再灌注120 min心律失常评分均低于I/R组(4.5±0.6 vs.2.1±0.4,3.7±0.5 vs.1.1±0.3,P均<0.05)。与SO组比较,I/R组、DEX组心肌组织Cav1.2和NCX的mRNA水平均升高,而DEX组较I/R组明显降低(P均<0.05)。结论右美托咪定预处理可减少缺血再灌注心律失常发生,与减少Cav1.2和NCX的mRNA水平,抑制钙超载有关。

Objective To investigate effects and mechanisms of dexmedetomidine preconditioning on ischemia-reperfusion arrhythmia in rats.Methods From March to June 2015 in Basic Mesical College of Wuhan University,30 rats were divided into sham operation group（SO group）,ischemia-reperfusion group（I/R group） and dexmedetomidine preconditioning group（DEX group）,10 rats each group.Firstly,the coronary artery was ligated for 30 rain to cause myocardial ischemia,and then the ligature was loosened for 120 min to give the myocardium reperfusion.Lines were given but not ligated in SO group,100 μg/kg Dexmedetomidine was given intra-peritoneal at 2h before ischemia in DEX group,and the same volume physiological saline was given in I/R group.The type and the scores of arrhythmia were monitored and recorded in each group.The mRNA level of Cav1.2 and NCX were detected by the real-time PCR.Results There was no significant changes of cardiac rhythm in SO group,and the score of arrhythmia was 0.The incidence of arrhythmia were lower in DEX group than in I/R group（P〈0.05）,and the scores of arrhythmia within 30 min of ischemia and 120 min of reperfusion in DEX group were both lower than in I/R group（P〈0.05）.Compared with SO group,the mRNA levels of Cav1.2 and NCX increased in both I/R group and DEX group（P〈0.05）,and which were significantly lower in DEX group than in I/R group.Conclusion Dexmedetomidine preconditioning can reduce the incidence of arrhythmia,which is related to the mechanism that dexmedetomidine reduces Cav1.2 and NCX mRNA levels to inhibit calcium overload.