摘要
目的:探讨调控PDGF/PDGFR通路对心肌缺血再灌注损伤(MI/RI)后心室重构的作用及相关机制。方法:建立小鼠MI/RI模型,在PDGFR磷酸化抑制剂CP-673,451干预后,采用心脏超声心超检测心功能,Masson染色检测心肌纤维化,qPCR法测定炎症因子的表达;分离新生大鼠心肌成纤维细胞(neonatal rat cardic fibroblasts,NCF),采用qPCR分析其胶原合成基因的表达,Western印迹法分析p38分子磷酸化水平。结果:CP-673,451可改善小鼠MI/RI后LVEF、FS、LVIDs等心功能指标(P<0.05),减轻MI/RI后心肌纤维化程度;CP-673,451可有效抑制MI/RI后梗死处心肌内炎症因子IL-1β,TNF-α,IL-6 mRNA表达水平(P<0.05),降低NCF中PDGF-BB导致的ColⅠ及ColⅢmRNA的升高程度(P<0.05),降低PDGF-BB刺激的p38蛋白磷酸化水平(P<0.05)。结论:在MI/RI过程中,抑制PDGF/PDGFR通路可下调梗死心肌中炎症反应和胶原合成,从而改善心室重构,这可能通过p38/MAPK信号通路发挥作用。
Objective:To explore the effect of platelet derived growth factor(PDGF)/PDGF receptor(PDGFR)pathway on ventricular remodeling after myocardial ischemia-reperfusion injury(MI/RI)and the underlying mechanisms.Methods:A MI/RI mouse model was established,and cardiac function was detected by cardiac ultrasonography,myocardial fibrosis was detected by Masson staining,and the expression of inflammatory factors was determined by quantitative polymerase chain reaction(qPCR)with the intervention of PDGFR phosphorylation inhibitor CP-673,451.The neonatal rat cardiac fibroblasts(NCF)were isolated.The expression of collagen synthesis genes was analyzed by qPCR,and the phosphorylation level of p38 molecule was analyzed by Western blot.Results:CP-673,451 can improve the cardiac function index of left ventricular ejection fraction(LVEF),fraction shortening(FS),and left ventricular internal diameter(LVID)after MI/RI in mice(P<0.05),and reduce the degree of myocardial fibrosis after MI/RI;CP-673,451 can effectively inhibit the expression of inflammatory factors interleukin(IL)-1β,tumor necrosis factor(TNF)-α,IL-6 mRNA in myocardial infarction after MI/RI(P<0.05),reduce the increase of ColⅠand ColⅢmRNA caused by PDGF-BB in NCF(P<0.05),and reduce p38 protein phosphorylation level stimulated by PDGF-BB(P<0.05).Conclusions:Inhibiting the PDGF/PDGFR pathway during MI/RI can down-regulate the inflammatory response and collagen synthesis in the infarcted myocardium,thereby improving ventricular remodeling,which may play a role via the p38/MAPK signaling pathway.
作者
侯士强
陈莎莎
刘杰
李新明
HOU Shi-qiang;CHEN Sha-sha;LIU Jie;LI Xin-ming(Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai 200032, China;Department of Cardiothoracic Surgery, Shanghai East Hospital, Tongji University, Shanghai 200120, China;School of Medicine, Tongji University, Shanghai 200092, China)
出处
《中国临床医学》
2020年第3期428-432,共5页
Chinese Journal of Clinical Medicine
基金
上海市自然科学基金(14ZR1437200).
