CircRNA Hipk1调控miR-146a-5p/Notch2轴对缺血性心律失常大鼠心肌细胞凋亡的影响  

Effect of CircRNA Hipk1 on Cardiomyocytes Apoptosis in Rats with Ischemic Arrhythmia by Regulating miR-146a-5p/Notch2 Axis

作　　者：郭亮[1] 李亚洁[1] GUO Liang;LI Yajie(Baoji Central Hospital,Baoji 721008,Shaanxi,China)

机构地区：[1]宝鸡市中心医院,陕西宝鸡721008

出　　处：《中西医结合心脑血管病杂志》2023年第4期643-648,654,共7页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的:探讨CircRNA Hipk1调控miR-146a-5p/Notch2轴对缺血性心律失常大鼠心肌细胞凋亡的影响。方法:将SD大鼠随机分为假手术组、模型组、CircRNA Hipk1 siRNA腺相关病毒(干扰CircRNA Hipk1)组、miR-146a-5p Antagomir(miR-146a-5p抑制剂)组、CircRNA Hipk1 siRNA腺相关病毒+miR-146a-5p Antagomir组、阴性对照(CircRNA Hipk1 siRNA腺相关病毒阴性对照+miR-146a-5p Antagomir阴性对照)组,每组12只;除假手术组外,其余各组制备缺血性心律失常模型,分组给药干预后,测定各组大鼠心律失常症状并进行评分;以2,3,5-氯化三苯基四氮唑(TTC)染色检测各组大鼠心肌梗死面积;苏木精-伊红(HE)染色检测各组大鼠心肌组织病理形态;采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(TUNEL)染色检测各组大鼠心肌细胞凋亡率;试剂盒检测各组大鼠血清致炎因子白细胞介素(IL)-1β、IL-17水平;逆转录实时定量聚合酶链式反应(RT-qPCR)检测各组大鼠心肌组织CircRNA Hipk1、miR-146a-5p及Notch2 mRNA表达水平。结果:与假手术组比较,模型组大鼠心肌组织结构紊乱,细胞轮廓不清,排列紊乱,有炎性细胞浸润,呈明显损伤,心律失常评分、心肌梗死面积、心肌细胞凋亡率、血清IL-1β与IL-17水平、心肌组织CircRNA Hipk1、Notch2 mRNA表达水平升高(P<0.05),miR-146a-5p表达水平降低(P<0.05)。与模型组、CircRNA Hipk1 siRNA腺相关病毒+miR-146a-5p Antagomir组比较,CircRNA Hipk1 siRNA腺相关病毒组大鼠心肌组织病理损伤减轻,心律失常评分、心肌梗死面积、心肌细胞凋亡率、血清IL-1β与IL-17水平、心肌组织CircRNA Hipk1、Notch2 mRNA表达水平降低(P<0.05),miR-146a-5p表达水平升高(P<0.05);miR-146a-5p Antagomir组大鼠心肌组织病理损伤加重,心律失常评分、心肌梗死面积、心肌细胞凋亡率、血清IL-1β与IL-17水平、心肌组织CircRNA Hipk1、Notch2 mRNA表达水平升高(P<0.05),miR-146a-5p表达水平降低(P<0.05)。�Objective: To investigate the effect of CircRNA Hipk1 on cardiomyocytes apoptosis in rats with ischemic arrhythmia by regulating miR-146a-5p/Notch2 axis.Methods: The SD rats were randomly divided into sham group, model group, CircRNA Hipk1 siRNA adeno-associated virus(interference CircRNA Hipk1) group, miR-146a-5p Antagomir(miR-146a-5p inhibitor) group, CircRNA Hipk1 siRNA gland-associated virus+miR-146a-5p Antagomir group, and negative control(CircRNA Hipk1 siRNA adeno-associated virus negative control+miR-146a-5p Antagomir negative control) group, with 12 rats in each group.Ischemic arrhythmia models of rats were prepared except for the sham group.After the intervention, the arrhythmia symptoms of rats in each group were evaluated and scored.Myocardial infarct area was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining;myocardial histopathologic data was measured by hematoxylin-eosin(HE) staining;terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay(TUNEL) staining was used to measure cardiomyocytes apoptosis in each group.The apoptosis rate of cardiomyocytes was measured by TUNEL staining.The levels of serum interleukin(IL)-1β and IL-17 were measured by the kit.The expressions of CircRNA Hipk1,miR-146a-5p, and Notch2 mRNA were measured by reverse transcription real-time quantitative polymerase chain reaction(RT-qPCR) in the myocardial tissue of rats.Results: Compared with the sham group, the myocardial tissue in the model group was disorganized with poorly defined and disorganized cell outlines, infiltrated with inflammatory cells, showing significant damage, with increased arrhythmia score, myocardial infarct area, myocardial apoptosis rate, serum IL-1β and IL-17 levels, and myocardial tissue CircRNA Hipk1 and Notch2 mRNA expressions(P<0.05),while the expressions of miR-146a-5p were decreased(P<0.05).Compared with the model group and CircRNA Hipk1 siRNA adeno-associated virus+miR-146a-5p Antagomir group, myocardial histopathological injury was reduced in the CircRNA Hipk1 si

关 键 词：缺血性心律失常 CircRNA Hipk1 miR-146a-5p/Notch2 心肌细胞 凋亡 大鼠 实验研究 

分 类 号：R541.7[医药卫生—心血管疾病]