肝素结合性表皮生长因子在糖尿病心肌病大鼠心肌纤维化中的作用  

The effect of heparin binding epidermal growth factor on myocardial fibrosis in rats with diabetic cardiomyopathy

作　　者：张芬[1] 吴杰 董扬[1] ZHANG Fen;WU Jie;DONG Yang(Department of Cardiology,Jinhua People's Hospital,Jinhua 321000,China)

机构地区：[1]金华市人民医院心内科,321000

出　　处：《心电与循环》2022年第3期221-225,230,共6页Journal of Electrocardiology and Circulation

基　　金：金华市科学技术局公益类项目(2018-4-051)。

摘　　要：目的探讨肝素结合性表皮生长因子(HB-EGF)在糖尿病心肌病(DCM)大鼠心肌纤维化中的作用。方法选用8周龄Sprague-Dawley雄性大鼠20只,采用随机数字表法分成两组,DCM组高脂饲料喂养6周后,经腹腔注射40 mg/kg链脲佐菌素(单次)诱导糖尿病模型(餐后2 h血糖16.8 mmol/L),继续以高脂饲料喂养;对照组经腹腔注射对应量的柠檬酸盐缓冲液。分别在实验第8、12、14周每组各处死1只大鼠,观察左心室大小及心肌结构,14周时DCM组大鼠均经心脏超声检查证实左心室扩大认为DCM造模成功。比较两组大鼠体重、餐后2 h血糖水平;HE染色或Masson染色后显微镜下观察大鼠心肌组织;蛋白质印迹法及酶联免疫吸附测定法检测HB-EGF水平;聚合酶链式反应法测定大鼠心肌HB-EGF mRNA表达水平。结果与对照组比较,DCM组大鼠体重、餐后2 h血糖水平均降低(均P<0.01);14周时,DCM组左心室收缩末期内径指数[(13.6±2.1)mm比(8.7±0.6)mm]、左心室舒张末期内径指数[(22.1±4.5)mm比(14.5±1.4)mm]均升高,左心室射血分数(LVEF)[(65.3±4.9)%比(79.8±4.3)%]降低(均P<0.05)。DCM组心肌细胞肿胀、排列紊乱,纤维化明显;血清及心肌组织HB-EGF水平升高,HB-EGF mRNA表达水平升高(均P<0.05)。结论HB-EGF高表达可促进DCM大鼠的心肌纤维化。Objective To investigate the effect of heparin binding epidermal growth factor(HB-EGF)on myocardial fibrosis in rats with diabetic cardiomyopathy(DCM).Methods Twenty eight-week-old sprague-dawley male rats were randomly divided into model group and control group.Model group was fed high-fat diet and then received40 mg/kg streptozotocin intraperitoneal injection(single dose)at the sixth week to induce diabetes.The control group was fed with routine diet and received the corresponding amount of citrate buffer intraperitoneal injection.One rat was sacrificed at 8 weeks,12 weeks and 14 weeks,respectively,in every group and left ventricular size and myocardial fibrosis were assessed.At the fourteenth week left ventricle enlargement was determined by echocardiography and DCM was established in all rats in model group.Body weight and 2-h postprandial blood glucose were measured.Myocardial tissues were observed under a microscope using HE staining or Masson staining.The expression of HB-EGF protein was detected by western blotting and enzyme-linked immunosorbent assay(ELISA),and myocardial HB-EGF mRNA was detected by PCR.Results The body weight was significantly lower and postprandial blood glucose was significantly higher in model group than in the control group(all P<0.01).Left ventricular end systolic diameter index and diastolic diameter index were significantly higher and left ventricular ejection fraction was significantly lower in model group than in the control group[(13.6±2.1)mm vs.(8.7±0.6)mm,(22.1±4.5)mm vs.(14.5±1.4)mm,(65.3±4.9)%vs.(79.8±4.3)%,respectively.(all P<0.05)].Myocardial swelling,disorganization and fibrosis were observed in model group.Serum HB-EGF myocardial HB-EGF mRNA were significantly higher in model group than in the control group(all P<0.05).Conclusion The expression of HB-EGF is increased in myocardial tissue of rat with diabetic DCM.

关 键 词：肝素结合性表皮生长因子 糖尿病心肌病 心肌纤维化 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]