曲美他嗪对大鼠心肌缺血再灌注损伤的影响及机制  

Effect and mechanism of trimetazidine on myocardial ischemia-reperfusion injury in rats

作　　者：鲁成昊 张成鑫[1] 郭志祥[1] 葛圣林[1] LU Cheng-hao;ZHANG Cheng-xin;GUO Zhi-xiang;GE Sheng-lin(Department of Cardiouascular Surgery,The First Afiliated Hospital of Anhui Medical University,Hefei 230031,An-hui,China)

机构地区：[1]安徽医科大学第一附属医院心脏大血管外科,合肥230031

出　　处：《医学研究生学报》2021年第11期1158-1162,共5页Journal of Medical Postgraduates

摘　　要：目的目前关于曲美他嗪对心肌缺血再灌注损伤(MIVR)的干预作用研究较少,且机制尚不明确。文中旨在探讨曲美他嗪对大鼠MI/R的影响及相关机制。文中旨在建立MI/R大鼠模型,通过Tunel染色及免疫印迹法观察大鼠心肌细胞凋亡及相关通路蛋白表达量的变化。方法40只大鼠中随机抽取10只仅做假手术作为对照组,其余30只建立MI/R模型,随机分为MI/R组(同对照组尾静脉注射等体积葡萄糖溶液,腹腔注射等体积DMSO溶液)、曲美他嗪组(在缺血30min时尾静脉注射曲美他嗪葡萄糖溶液)、曲美他嗪+AC490组(在缺血30min时尾静脉注射曲美他嗪葡萄糖溶液,并腹腔注射AG490 DMSO溶液),每组10只。检测各组氧化应激指标;Tunel染色法检测心肌组织细胞凋亡率;免疫印迹法检测心肌组织Janus蛋白酪氨酸激酶2/信号转导及转录激活子3(JAK2)、p-JAK2信号转导及转录激活子3(STAT3)、p-STAT3蛋白表达量。结果与对照组、曲美他嗪组比较,MI/R组心肌组织丙二醛含量升高,SOD含量降低(P<0.05);与曲美他嗪组比较,曲美他嗪+AG490组心肌组织丙二醛含量升高,SOD含量降低(P<0.05)。与对照组、曲美他嗪组心肌组织细胞凋亡率[(6.87±0.82)%、(12.07±2.30)%]比较,MI/R组[(23.10±4.77)%]明显升高(P<0.05);与曲美他嗪组比较,曲美他嗪+AG490组心肌组织细胞凋亡率[(16.61±3.12)%]明显升高(P<0.05)。与MI/R组比较,曲美他嗪组心肌组织p-JAK2/JAK2、p-STAT3/STAT3明显升高(P<0.05),对照组明显降低(P<0.05);与曲美他嗪组比较,曲美他嗪+AC490组p-JAK2/JAK2、p-STAT3/STAT3明显降低,(P<0.05)。结论曲美他嗪可减轻MI/R大鼠氧化应激反应,减少心肌细胞凋亡,其作用机制可能与激活JAK2/STAT3信号通路有关。Objective As there are few studies on the intervention ffeet of trimetazidine on myocardial ischemia-reperfusion injury(ML/R),and its mechanism is still unclear at present,this article is to explore the efects and related mechanisms of trimetazi-dine on myocardial ischemia-reperfusion injury(MI/R)in rats.This article intends to establish a MI/R rat model,and observe the changes of cardiomyocyte apoptosis and related pathway protein expression in rats by Tunel staining and immunoblotting.Methods Ten out of 40 rats were randomly selected for sham operation as the Control group,and the remaining 30 rats were established with MI/R models.They were randomly divided into MI/R group,trimetazidine group,trimetazidine+AG490 group,10 rats in each group.In the trimetazidine group,the glucose solution of trimetazidine was injected into the tail vein at a dose of2 mg·kg^(-1)at 30 minules of is-chemia.In the trimetazidine±AC490 group,the glucose solution of trimetazidine was injeeted into the tail vein at a dose of2 mg·kg^(-1)at 30 minutes of ischemia.AG490 DMSO solution was injected intraperitoneally at a dose of 5 mg·kg^(-1)at the time of 30 minutes of ischemia.Control.group and MI/R group were given an equal volume of glucose solution and intraperitoneally injected an equal volume of DMSO solution.The oxidative stress indicators were:detected in each group.The apoptosis rate of myocardial tissue were detected by Tunel staining method.The protein expression of Janus protein tyrosine kinase 2/signal transducer and activator of transcription 3(JAK2),p-JAK2,signal transducer and activator of transcription 3(STAT3)and p-STAT3 in myocardial isse were detected by W estern blotting.Results The levels of malondialdehyde(MDA)in myocardial tissue in the Control group,MI/R group,trimelazidine group,and trimetazidine±AG490 group were(1.94±0.27)nmol·mg^(-1)(8.16±0.73)nmol·mg^(-1),(4.26±0.51)nmol·mg^(-1),(6.01±0.70)nmol·mg^(-1).The levels of superoxidedismutase(S0D)in myo-cardial isse in the four groups were(32.14±5.36)U·g^

关 键 词：曲美他嗪 心肌缺血再灌注损伤 Janus蛋白酪氨酸激酶2 信号转导及转录激活子3 

分 类 号：R541[医药卫生—心血管疾病]