过表达双特异性蛋白磷酸酶1通过调节自噬作用减轻阿霉素诱导的心肌细胞凋亡和心肌纤维化  

Overexpression of Dual-Specificity Protein Phosphatase 1 Reduces Adriamycin Induced Cardiomyocyte Apoptosis and Myocardial Fibrosis by Regulating Autophagy

作　　者：胡丽君 魏燕 贺行巍 张洁 HU Lijun;WEI Yan;HE Xingwei;ZHANG Jie(Department of Cardiovascular Medicine,Hubei Jianghan Oilfield General Hospital,Jianghan,Hubei 433124,China;Department of Cardiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Laboratory Medicine,Hubei Jianghan Oilfield General Hospita,Jianghan,Hubei 433124,China)

机构地区：[1]湖北江汉油田总医院心血管内科,湖北江汉433124 [2]华中科技大学同济医学院附属同济医院心血管内科,武汉430030 [3]湖北江汉油田总医院检验科,湖北江汉433124

出　　处：《岭南心血管病杂志》2023年第2期190-197,共8页South China Journal of Cardiovascular Diseases

基　　金：湖北省卫生健康委科研立项项目(项目编号:WJ2019Q058)。

摘　　要：目的探讨过表达双特异性蛋白磷酸酶1(dual-specificity protein phosphatase 1,DUSP1)对阿霉素(adriamycin,ADR)诱导的心肌细胞凋亡和心肌纤维化的影响及作用机制。方法将SD大鼠随机分为对照组、ADR组、ADR+Ad-DUSP1组、ADR+Ad-NC组,每组10只。采用超声心动图检测大鼠心功能参数左心室舒张末内径值(left ventricular end diastolic diameter,LVEDD)、左心室收缩末内径值(left ventricular end systolic diameter,LVESD)、左心室射血分数(left ventricular ejection fraction,LVEF)和左心室短轴缩短率(left ventricular fractional shortening,LVFS)。实时定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)法检测大鼠心肌组织中DUSP1 mRNA表达,苏木素-伊红(hematoxylin-eosin,HE)染色、TUNEL染色及Masson染色分别检测大鼠心肌组织病理形态学变化、心肌细胞凋亡和心肌纤维化,Western blot法检测大鼠心肌组织相关蛋白表达。结果对照组、ADR组、ADR+Ad-DUSP1组和ADR+Ad-NC组大鼠心肌组织中DUSP1 mRNA表达水平分别为1.00±0.10、0.23±0.02、0.22±0.02、0.76±0.08。与对照组比较,ADR组大鼠心肌组织中DUSP1 mRNA表达水平显著降低;心功能指标LVEDD、LVESD显著升高,LVEF和LVFS显著降低;心肌组织可见明显病理损伤,心肌细胞凋亡率和胶原容积分数(collagen volume fraction,CVF)显著升高;心肌组织中B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)蛋白表达量显著降低,B淋巴细胞瘤-2相关蛋白(B-cell-lymphoma-2 related protein,Bax)、切割型半胱氨酸天冬氨酸蛋白水解酶-3(cleaved caspase-3)、Ⅰ型胶原蛋白(typeⅠcollagen,COL-Ⅰ)、Ⅲ型胶原蛋白(typeⅢcollagen,COL-Ⅲ)、基质金属蛋白酶2(matrix metalloproteinase 2,MMP-2)、转化生长因子-β1(transforming growth factorβ1,TGF-β1)蛋白表达量显著升高;心肌组织中微管相关蛋白轻链3(microtubule associated protein light chain 3,LC3)、Beclin-1蛋白表达量显著升高、P62蛋白表达量显著降低,Objectives To investigate the effect and mechanism of overexpression of bispecific protein phosphatase 1(DUSP1)on cardiomyocyte apoptosis and myocardial fibrosis induced by adriamycin(ADR).Methods SD rats were randomly divided into control group,ADR group,ADR+Ad-DUSP1 group and ADR+Ad NC group,with 10 rats in each group.Left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD),left ven⁃tricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)of rats were detected by echocardiog⁃raphy.The expression of DUSP1 mRNA in rat myocardium was detected by quantitative real time polymerase chain reac⁃tion(qRT-PCR).The pathomorphological changes,cardiomyocyte apoptosis and myocardial fibrosis of rat myocardium⁃were detected byhematoxylin-eosin(HE)staining,TUNEL staining and Masson staining,and the expression of related proteins in rat myocardium was detected by Western-blot.Results The expressions of DUSP1 mRNA in control group,ADR group,ADR+Ad-DUSP1 group and ADR+Ad NC group respectively were 1.00±0.1,0.23±0.02,0.22±0.02 and 0.76±0.08.Compared with control group,the expression of DUSP1 mRNA in myocardial tissue of ADR group significantly decreased;The cardiac function indexes LVEDD and LVESD significantly increased,while LVEF and LVFS signifi⁃cantly decreased;The myocardial tissue was obviously damaged,myocardial cell apoptosis rate and collagen volume fraction(CVF)significantly increased;The expression of B-cell lymphoma-2(BCL-2)in myocardium significantly decreased,and the expressions of B-cell lymphoma-2 related protein(Bax),cleaved caspase-3,typeⅠcollagen(COL-Ⅰ),typeⅢcollagen(COL-Ⅲ),matrix metalloproteinase 2(MMP-2),transforming growth factorβ1(TGF-β1)increased significantly;The expressions of microtubule associated protein light chain 3(LC3)and Beclin-1 protein in myocardium significantly increased,while expression of P62 protein significantly decreased;The differences were statisti⁃cally significant(P<0.05).Compared with ADR group,the

关 键 词：心肌损伤 双特异性蛋白磷酸酶1 阿霉素 细胞凋亡 纤维化 自噬 

分 类 号：R542[医药卫生—心血管疾病]