右美托咪定预处理对糖尿病大鼠心肌缺血-再灌注损伤的作用和机制  

Effect and mechanism of dexmedetomidine preconditioning against myocardial ischemia/reperfusion injury in diabetic rats

作　　者：张世平[1] 沈鑫[2] 李会玲[3] 景桂霞[4] 杨瑞[1] 金梅梅[3] 常建华 ZHANG Shiping;SHEN Xin;LI Huiling;JING Guixia;YANG Rui;JIN Meimei;CHANG Jianhua(Department of Anesthesiology,Shanxi Provincial People＇s Hospital,Xi＇an 710068,China)

机构地区：[1]陕西省人民医院麻醉科,西安市710068 [2]陕西省人民医院医务处,西安市710068 [3]西安交通大学医学院第一附属医院急诊科 [4]西安交通大学医学院第一附属医院麻醉科

出　　处：《临床麻醉学杂志》2018年第7期707-711,共5页Journal of Clinical Anesthesiology

基　　金：陕西省社会发展科技攻关项目(2015SF103)

摘　　要：目的探讨右美托咪定(Dex)预处理对糖尿病大鼠心肌缺血-再灌注损伤(MIRI)的作用及其机制。方法诱导建立糖尿病模型大鼠40只,体重150~170g,8周后随机分为四组:假手术组(S组),缺血-再灌注组(IR组),缺血-再灌注+Dex给药组(IRD组),缺血-再灌注+育亨宾与Dex复合给药组(IRYD组),每组8只。S组和IR组以等量生理盐水作预处理,IRD组先以5μg/kg的速度输注Dex 10 min,后以5μg·kg-1·h-1的速率再输注60 min,IRYD组先静脉输注1mg/kg的育亨宾,15min后改为0.5mg·kg-1·h-1继续输注60min,育亨宾开始输注5min后以与IRD组相同的方法输注Dex。除假手术组外,各组均采用结扎-放松大鼠冠状动脉左前降支的方法使局部心肌缺血30min、继而再灌注2h。分别记录缺血前(T0)、结扎30 min(T1)、再灌注1h(T2)和再灌注2h(T3)时的HR、左室收缩压(LVSP)、左室内压最大上升速率(+dp/dtmax)和左室内压最大下降速率(-dp/dtmax)和左室舒张末压(LVEDP);测定再灌注2h后的心肌梗死面积并检测血浆肌钙蛋白I(cTnI)含量和一氧化氮(NO)浓度。结果与S组、IR组和IRYD组比较,T0-T3时IRD组的HR明显减慢(P<0.05)。与IR组和IRYD组比较,T3时IRD组LVSP、+dp/dtmax和-dp/dtmax明显升高(P<0.05),LVEDP明显降低(P<0.05),IRD组缺血坏死区/缺血危险区(AN/AAR)明显缩小(P<0.05),cTnI含量明显降低(P<0.05),NO浓度明显升高(P<0.05)。T3时IRYD组与IR组大鼠各指标差异无统计学意义。结论 Dex预处理能改善糖尿病大鼠MIRI后的心脏收缩和舒张功能、减少心肌细胞坏死,其保护机制可能与α2受体激动和血浆NO浓度升高有关。Objective To investigate the effect and its mechanism of dexmedetomidine（Dex）preconditioning on myocardium following myocardial ischemia/reperfusion injury（MIRI）in diabetic rats.Methods Forty diabetic rats weighing 150-170 g were divided randomly into 4 groups after 8 weeks（n=8）：group S：sham operation group;group IR：myocardial ischemic reperfusion（IR）group;group IRD：IR＋Dex preconditioning group;group IRYD：IR＋yohimbine-Dex preconditioning.The rats of group S and IR were pretreated with the same amount of normal saline.The rats in group IRD were pretreated with Dex at a speed of 5μg/kg for 10 min firstly,then 5μg·kg-1·h-1 for60 min.The rats in group IRYD were pretreated with 1 mg/kg of yohimbine for 15 min firstly,then0.5 mg·kg-1·h-1 for 60 min.The infusion of yohimbine was 5 min earlier than the Dex in IRYD group.In addition to the group S,all the groups adopted ligation-relaxation of the left anterior descending branch of the coronary artery in rats to make local myocardial ischemia for 30 min and then reperfusion for 2 h.HR,LVSP,＋dp/dtmax,-dp/dtmaxand LVEDP were measured respectively to evaluate the cardiac systolic and diastolic function of the four points：before ischemic（T0）,ligation for30 min（T1）,reperfusion of 1 h（T2）and reperfusion of 2 h（T3）.The myocardial infarct sizes were evaluated after reperfusion of 2 h,while the content of cTnI and NO in plasma were quantified.Results Compared with the group S,group IR and group IRYD,HR in group IRD slowed down significantly from T0 to T3（P〈0.05）.Compared with the group IR and group IRYD,the LVSP,＋dp/dtmaxand-dp/dtmax were higher（P〈0.05）,LVEDP was lower（P〈0.05）,while the ratio of AN/AAR was smaller（P〈0.05）,the content of cTnI was lower（P〈0.05）and the concentration of NO higher in group IRD at T3（P〈0.05）.There was no statistically significant difference between the two groups of IR and IRYD at T3.Conclusion The preconditioning of Dex can improve the systolic and diastolic fu

关 键 词：右美托咪定 预处理 糖尿病大鼠 心肌缺血-再灌注损伤 心脏功能 一氧化氮机制 

分 类 号：R614[医药卫生—麻醉学]