达格列净预处理对心肌缺血再灌注损伤模型兔血清hs-cTnT、心肌结构及细胞凋亡的影响  

Effect of Dapagliflozin Pretreatment on Serum High-sensitive Cardiac Troponin T,Myocardial Structure and Apoptosis of Myocardial Ischemia-reperfusion Injury Model Rabbits

作　　者：李伟 马建群 朱玉红[2] LI Wei;MA Jianqun;ZHU Yuhong(Department of Cardiology,the Third Affiliated Hospital of Shandong First Medical University,Jinan 250031,China;Department of Pathology,Binzhou Medical University Hospital,Binzhou 256603,China)

机构地区：[1]山东第一医科大学第三附属医院心血管内科,济南250031 [2]滨州医学院附属医院病理科,山东滨州256603

出　　处：《医学综述》2022年第10期2044-2049,共6页Medical Recapitulate

摘　　要：目的探索达格列净预处理对心肌缺血再灌注损伤(MIRI)模型兔血清高敏心肌肌钙蛋白T(hs-cTnT)、心肌结构及细胞凋亡的影响。方法18只雄性成年新西兰大白兔依据随机数字表法分为假手术组、模型组和达格列净组,每组6只。假手术组:在兔的左前降支下方只穿线,不结扎;模型组:用缝合线穿绕兔心脏左前降支中、上1/3交界处并在此放置一束线后一起结扎,结扎40 min后再灌注120 min;达格列净组:结扎前20 min经兔耳缘静脉给予达格列净0.5 mg/kg。三组分别于结扎前、结扎40 min、再灌注120 min时留取血标本检测血清hs-cTnT水平;取缺血区心肌组织,观察各组心肌组织病理学变化;末端脱氧核苷酸转移酶介导的原位缺口末端标记(TUNEL)法观察细胞凋亡情况,通过阳性细胞计数评价凋亡情况。结果hs-cTnT不同时点间、组间的主效应差异有统计学意义(P<0.01),组间和时点间存在交互作用(P<0.01);结扎后40 min和再灌注120 min,模型组与达格列净组血清hs-cTnT均显著高于假手术组(均P<0.01),但达格列净组血清hs-cTnT明显低于模型组(P<0.01);模型组与达格列净组血清hs-cTnT均随着缺血及再灌注时间延长而增加(P<0.01)。与假手术组相比,模型组的心肌细胞形态改变和坏死严重;达格列净组的心肌细胞也有形态改变和坏死,但病变程度明显轻于模型组。假手术组、模型组、达格列净组凋亡指数分别为(10.0±0.9)%、(42.4±1.5)%、(28.6±1.2)%,与假手术组相比,模型组与达格列净组凋亡指数均增加(P<0.01),而与模型组相比,达格列净组凋亡指数降低(P<0.01)。结论达格列净预处理对缺血再灌注损伤心肌具有保护作用,其作用机制可能与减少心肌酶释放和心肌细胞凋亡有关。Objective To explore the effects of dapagliflozin pretreatment on serum high-sensitive cardiac troponin T(hs-cTnT),myocardial structure and cell apoptosis of myocardial ischemia-reperfusion injury(MIRI)model rabbits.Methods Eighteen male adult New Zealand rabbits were randomly divided into a sham-operated group,a model group,and a dapagliflozin group,with 6 rabbits in each group.In the sham-operated group,only a suture was threaded under the left anterior descending branch of the rabbit without ligation;in the model group,a suture was threaded around the upper middle third of the left anterior descending branch of the rabbit′s heart and a bundle of sutures was placed there and then ligated together,and the rabbit was reperfused for 120 min after ligation for 40 min;in the dapagliflozin group,dapagliflozin 0.5 mg/kg was given through the ear margin vein 20 min before ligation.The levels of hs-cTnT of the three groups were measured before ligation,40 min after ligation and 120 min after reperfusion;myocardial tissue was taken from the ischemic area to observe the histopathological changes in the myocardium of each group;terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)method was adopted to observe apoptosis and apoptosis levels were assessed by positive cell counts.Results The main effect difference of hs-cTnT at different time points and between groups was statistically significant(P<0.01),and there was interaction between groups and time points(P<0.01).After ligation for 40 min and reperfusion for 120 min,the serum hs-cTnT of the model group and dapagliflozin group was significantly higher than that of the sham-operated group(all P<0.01),but the serum hs-cTnT of dapagliflozin group was significantly lower than that of the model group(P<0.01).The serum hs-cTnT of the model group and dapagliflozin group increased with the prolonging of ischemia and reperfusion time(P<0.01).The model group had severe morphological alterations and necrosis of cardiomyocytes compared to the sham-operated g

关 键 词：心肌缺血再灌注损伤 钠-葡萄糖协同转运蛋白抑制剂 达格列净 

分 类 号：R542.2[医药卫生—心血管疾病]