右美托咪定预处理对大鼠心肌缺血/再灌注损伤时心肌组织内质网应激的影响  

Effects of dexmedetomidine preconditioning on endoplasmic reticulum stress during myocardial ischemia/reperfusion injury in rats

作　　者：王辉[1] 嵇富海[1] 孟晓文[1] 彭科[1] 张俊[1] Wang Hui;Ji Fuhai;Meng Xiaowen;Peng Ke;Zhang Jun(Department of Anesthesiology,the First Affiliated Hospital of Soochow University,Suzhou 215006,China)

机构地区：[1]苏州大学附属第一医院麻醉科,215006

出　　处：《国际麻醉学与复苏杂志》2020年第8期737-741,共5页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金(81671880);江苏省医学创新团队(CXTDA2017043);苏州市重点病种项目(LCZX201603)。

摘　　要：目的探讨右美托咪定(dexmedetomidine,Dex)预处理对大鼠心肌缺血/再灌注损伤(myocardial ischemia/reperfusion injury,MI/RI)时心肌组织内质网应激(endoplasmic reticulum stress,ERS)的影响。方法雄性SD大鼠45只,230~270 g,按随机数字表法分为3组(每组15只):假手术组(S组)、缺血/再灌注组(I/R组)、右美托咪定+缺血/再灌注组(D+I/R组)。采用结扎左冠状动脉前降支(left anterior descending coronary artery,LAD)30 min后松结再灌注6 h的方法构建MI/RI模型。Dex经右侧颈内静脉泵注,先以1.0μg‧kg-1‧h-1泵注10 min,再以0.7μg‧kg-1‧h-1泵注15 min。通过伊文蓝和2,3,5-氯化三苯基四氮唑(2,3,5-triphenyl tetrazolium chloride,TTC)双染色法检测心肌缺血面积及心肌梗死面积,实时荧光定量PCR(real-time quantitative PCR,RT-qPCR)检测心肌组织ERS相关分子葡萄糖调节蛋白78(glucose regulated protein 78,GRP78)、C/EBP同源蛋白(C/EBP homologous protein,CHOP)及炎症因子IL-1β、IL-6 mRNA的表达水平,Western blot检测心肌组织GRP78、CHOP、cleaved caspase-3蛋白相对表达量。结果与S组比较,I/R组和D+I/R组心肌梗死面积和心肌缺血面积增加(P<0.05),GRP78、CHOP、IL-1β、IL-6 mRNA水平升高(P<0.05),GRP78、CHOP、cleaved caspase-3蛋白相对表达量升高(P<0.05)。与I/R组比较,D+I/R组心肌梗死面积减少(P<0.05),GRP78、CHOP、IL-1β、IL-6 mRNA水平降低(P<0.05),GRP78、CHOP、cleaved caspase-3蛋白相对表达量降低(P<0.05)。结论Dex预处理可以有效抑制大鼠MI/RI时的ERS,减轻心肌细胞凋亡和炎症反应。Objective To investigate the effects of dexmedetomidine(Dex)preconditioning on endoplasmic reticulum stress(ERS)in myocardial tissues of rats during myocardial ischemia/reperfusion injury(MI/RI).Methods According to the random number table method,45 SD male rats(weighing 230-270 g)were divided into three groups(n=15):group sham operation(group S),group ischemia/reperfusion(I/R)and group Dex+ischemia/reperfusion(group D+I/R).An MI/RI model was established through occlusion of the left anterior descending coronary artery(LAD)for 30 min followed by reperfusion for 6 h.Dex was pumped into the right jugular vein at a rate of 1.0μg‧kg-1‧h-1 for 10 min,followed by 0.7μg‧kg-1‧h-1 for 15 min.The ischemic and infracted region size was measured by Evans blue and 2,3,5-triphenyl tetrazolium chloride(TTC)double staining.The mRNA level of endoplasmic reticulum stress related molecules such as glucose regulated protein 78(GRP78),C/EBP homologous protein(CHOP),and inflammatory factors interleukin(IL)-1βand IL-6 were detected by real-time quantitative PCR(RT-qPCR).Western blot was adopted to detect the expression of GRP78,CHOP and cleaved caspase-3.Results Compared with group S,the ischemic and infracted region size in groups I/R and D+I/R significantly increased(P<0.05),the levels of GRP78,CHOP,IL-1β,and IL-6 mRNA remarkably increased(P<0.05)and the levels of GRP78,CHOP and cleaved caspase-3 protein remarkably increased(P<0.05).Compared with group I/R,the infract size in group D+I/R significantly decreased(P<0.05),the levels of GRP78,CHOP,IL-1β,and IL-6 remarkably reduced(P<0.05)and the levels of GRP78,CHOP and cleaved caspase-3 protein remarkably reduced(P<0.05).Conclusions Dex preconditioning can effectively inhibit endoplasmic reticulum stress during MI/RI in rats,alleviating apoptosis and inflammation.

关 键 词：右美托咪定 心肌 缺血/再灌注损伤 内质网应激 炎症反应 凋亡 

分 类 号：R614[医药卫生—麻醉学]