双调蛋白对糖尿病心肌病大鼠心肌细胞凋亡和氧化应激的影响  

Effect of Amphiregulin on Apoptosis and Oxidative Stress in Cardiomyocyte of Diabetic Cardiomyopathy Rat

作　　者：舒芬 莫元曦 洪万紫 邵思思 刘耀新 李心怡 王心怡 程雨琪 蒋磊 谭宁[1,2] SHU Fen;MO Yuanxi;HONG Wanzi;SHAO Sisi;LIU Yaoxin;LI Xinyi;WANG Xinyi;CHENG Yuqi;JJIANG Lei;TAN Ning(Medical College of South China University of Technology,Guangzhou 510006,China;Department of Cardiology,Guangdong Cardiovascular Institute,Guangdong Provincial People′s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China)

机构地区：[1]华南理工大学医学院,广州510006 [2]广东省心血管病研究所南方医科大学附属广东省人民医院(广东省医学科学院)心内科,广州510080

出　　处：《岭南心血管病杂志》2023年第3期326-332,共7页South China Journal of Cardiovascular Diseases

基　　金：国家自然科学基金(项目编号:82170339)。

摘　　要：目的探讨双调蛋白(amphiregulin,AREG)对糖尿病心肌病大鼠心肌细胞凋亡和氧化应激的的影响。方法25 mmol/L葡萄糖和500μmol/L棕榈酸(HGHF)诱导大鼠心肌细胞(H9C2)18 h,建立体外糖尿病心肌病大鼠心肌细胞模型。采用实时定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)和蛋白质印迹(Western blotting,WB)检测AREG基因的表达,采用流式细胞分析和脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling,TUNEL)染色观察siRNA下调AREG后H9C2细胞凋亡和氧化应激情况。通过qRT-PCR检测心肌细胞肥厚和纤维化的分子水平。结果在HGHF处理的H9C2细胞中AREG表达上调。抑制AREG的表达,减轻了HGHF导致的大鼠心脏氧化应激的增强,且减少了心肌细胞的凋亡,改善了心肌肥厚和纤维化的分子指标。结论AREG下调通过抑制细胞氧化和细胞凋亡来缓解心肌损伤,AREG可以作为治疗糖尿病心肌病的分子靶标。Objectives To investigate the effect of amphiregulin(AREG)on apoptosis and oxidative stress in cardiomyocyte of diabetic cardiomyopathy rat.Methods Diabetic cardiomyopathy rat cardiomyocyte model was induced by 25 mmol/L glucose and 500μmol/L palmitic acid(HGHF)in rat cardiomyocytes(H9C2)for 18 hours.Quantitative real time polymerase chain reaction(qRT-PCR)and Western blotting(WB)were used to detect the expression of AREG gene.Flow cytometry and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling(TUNEL)staining was used to observe the apoptosis and oxidative stress of H9C2 cells after down regulation of AREG by siRNA.The molecular level of hypertrophy and fibrosis of cardiomyocytes were detected by qRT-PCR.Results AREG expression was up-regulated in HGHF-treated H9C2 cells.Inhibiting the expression of AREG alleviated the enhancement of oxidative stress induced by HGHF in rat heart,reduced the apoptosis of myocardial cells,and improved the molecular indicators of myocardial hypertrophy and fibrosis.Conclusions AREG down-regulation can alleviate myocardial injury by inhibiting oxidation and apoptosis.AREG may be a molecular target for the treatment of diabetic cardiomyopathy in the future.

关 键 词：糖尿病心肌病 双调蛋白 凋亡 氧化应激 

分 类 号：R542[医药卫生—心血管疾病]