摘要
目的:分析血小板源性生长因子(PDGF)/蛋白激酶B(AKT)通路在压力超负荷诱导的心室重构中的作用及机制。方法:选取C57BL/6雌性小鼠55只,建立主动脉弓缩窄模型,成功建模45只,小鼠随机数字表法分为假手术组、DMSO组和实验组,假手术组小鼠开胸后逐层缝合,不进行主动脉缩窄术(TAC),开胸24 h后给予PBS溶液200μL加DMSO 50μL,DMSO组TAC术后24 h给予PBS溶液200μL加DMSO 50μL,实验组TAC术后24 h给予PBS溶液200μL加抑制剂AG129650μL,观察小鼠心功能及心肌组织病理形态。慢病毒感染建立PDGF基因不同表达人脐静脉内皮细胞(HUVEC)细胞鉴定和培养,依据细胞不同处理方式分为对照组、PDGF组、shRNA组和PDGF+IMA组,检测p-AKT及t-AKT蛋白在HUVEC细胞内表达情况。结果:DMSO组小鼠左室收缩末期容积(LVESV)、左室舒张末期容积(LVEDV)、左室收缩末期内径(LVESD)及左室舒张末期内径(LVEDD)较假手术组升高,左室射血分数(EF)、左室短轴缩短率(FS)较假手术组降低。实验组LVESV、LVEDV、LVESD及LVEDD较DMSO组降低,EF、FS较DMSO组升高,差异有统计学意义(P<0.05)。假手术组小鼠心肌组织整齐排列,间隙正常;DMSO组小鼠形态不规整,炎性细胞浸润,细胞间隙变大,胞核深染。实验组小鼠膨大或坏死细胞减少,间隙变小,炎性浸润降低。DMSO组小鼠心肌细胞横截面积较假手术组升高,实验组小鼠心肌细胞横截面积较DMSO组降低,差异有统计学意义(P<0.05)。PDGF+IMA组细胞内p-AKT及t-AKT蛋白表达较PDGF组及shRNA组显著降低,差异有统计学意义(P<0.05)。结论:PDGF可加速压力超负荷诱导心室重构,促进形成心肌组织纤维化,而抑制PDGF/AKT通路可改善心肌细胞肥大。
AIM:To analyze the role and mechanism of PDGF/AKT pathway in pressure overload-induced ventricular remodeling.METHODS:A total of 55 C57BL/6 female mice were selected to establish aortic arch narrowing model.Forty-five models were successfully modeled.The randomized digital table method was used to divide the models into sham operation group,DMSO group and experimental group.The sham operation group was opened after chest operation.The suture was performed without aortic coarctation(TAC).After 24 hours of thoracotomy,200μL of PBS solution and 50μL of DMSO were administered.The DMSO group was given 200μL of PBS solution and 50μL of DMSO 24 h after operation.The experimental group was given PBS solution 200μL plus AG129650μL 24 h after TAC to observe the heart function and myocardial histopathology of mice.Lentiviral infection was established to identify and culture HUVEC cells with different expression of PDGF gene.According to different treatments,the cells were divided into control group,PDGF group,shRNA group and PDGF+IMA group to detect the expression of p-AKT and t-AKT protein in HUVEC cells.RESULTS:LVESV,LVEDV,LVESD and LVEDD were increased in DMSO group as compared with sham operation group,while EF and FS of DMSO group were lower than those in sham operation group.LVESV,LVEDV,LVESD and LVEDD were lower in experimental group than those in DMSO group,while EF and FS in experimental group were higher than those in DMSO group.The difference was statistically significant(P<0.05).The sham operation group had neatly arranged myocardial tissue and normal interstitial;the DMSO group had irregular morphology,inflammatory cell infiltration,cell gap was enlarged,and the nucleus was deeply stained.The number of expanded or necrotic cells in experimental group decreased,the gap became smaller,and the inflammatory infiltration decreased.The cross-sectional area of myocardial cells in DMSO group was higher than that in sham operation group.The cross-sectional area of the myocardial cells in experimental group was low
作者
郑三福
郭伟溪
骆锦忠
覃水庆
ZHENG Sanfu;GUO Weixi;LUO Jinzhong;QIN Shuiqing(Department of Cardiology,the First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian,China;Department of Thoracic Surgery,the First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian,China;Department of Hematology,the First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian,China;Nanning Central Blood Station,Nanning 530007,Guangxi,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2020年第2期167-173,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
广西壮族自治区卫生厅科研项目(Z2011272)
关键词
血小板源性生长因子
压力超负荷
心肌纤维化
心室重构
心肌肥大
platelet-derived growth factor
pressure overload
myocardial fibrosis
ventricular remodeling
cardiac hypertrophy
