【摘要】 目的 研究色素上皮衍生因子(pigment epithelium-derived factor,PEDF)基因转染对大鼠缺血心脏功能的影响,并探讨其可能的作用机制。方法 采用冠状动脉左前降支结扎法建立大鼠心肌梗死模型,将72只Sprague-Dawley大鼠随即分为6组(每组12只):正常(Normal)组,转染PEDF-siRNA-LV(Infarct+siPEDF)组,转染PEDF-LV(Infarct+PEDF)组,载体对照(Infarct+vector)组,溶剂对照(Infarct+solvent)组,单纯梗死(Infarct)组。病毒转染4周后,超声心动图检测大鼠心脏功能,取各组心肌组织检测心肌局部炎症反应、心肌细胞和内皮细胞凋亡指数。结果 超声心动图检测显示:模型建立4周时,与Infarct+vector组、Infarct+solvent组及Infarct组相比,Infarct+siPEDF组左心室射血分数(left ventricular ejection fraction,LVEF)显著降低,Infarct+PEDF组LVEF显著升高,差异有统计学意义(P<0.05)。苏木精-伊红(H-E)染色检测局部炎症反应显示:与Infarct+vector组、Infarct+solvent组及Infarct组相比,Infarct+siPEDF组炎症细胞浸润显著增多,TNF-1α及TNFR1表达量显著增加,差异有统计学意义(P<0.05);Infarct+PEDF组炎症细胞浸润显著减少,TNF-1α表达量显著减少,差异有统计学意义(P <0.05),而TNFR1表达无显著变化。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling,TUNEL)检测细胞凋亡显示:与各对照组相比,Infarct+siPEDF组内皮细胞凋亡显著减少,心肌细胞凋亡显著增加;Infarct+PEDF组内皮细胞凋亡数量显著增加,而心肌细胞凋亡数量显著减少,差异均有统计学意义(P<0.05)。结论 PEDF可通过降低局部炎症和保护心肌细胞而改善缺血心脏功能。更多还原

【Abstract】 Objective To investigate the effect of pigment epithelium-derived factor(PEDF) on cardiac function and relevant mechanisms in rat ischemic heart.Methods Myocardial infarction model was established by left anterior descending coronary artery ligation and the 72 Sprague-Dawley rats were randomly divided into 6 groups(n=12 each):Normal,PEDF-RNAi-LV transfection group(Infarct+siPEDF),PEDF-LV transfection group(Infarct+PEDF),Infarct+vector group,Infarct+solvent group,Infarct group.Cardiac function was assessed bv echocardiography,the number of inflammatory cells were detected by hematoxylin and eosin(H-E) staining.Cardiomyocyte apoptosis and endothelial cell apoptosis were detected by terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL).PEDF,inflammatory-related proteins were tested by Western blot analysis.Results Echocardiography studies showed that left ventricular ejection fraction(LVEF)were significantly increased in Infarct+PEDF group compared with other groups(with exception of normal group)(P <0.05);but LVEF were significantly decreased in Infarct+siPEDF group compared with other groups(P <0.05).H-E staining and Western blott showed that inflammatory cell infiltration and expression of TNF-1α and TNFR1 was significantly increased in Infarct+siPEDF group compared with other groups(P <0.05),while inflammatory cell infiltration and expression of TNF-1α in Infarct+PEDF group reduced significantly compared with Infarct+vector group,Infarct+solvent group and Infarct group(P <0.05),there was no significant change in expression of TNFR1.TUNEL staining showed that the number of endothelial cell apoptosis wase increased significantly,but the number of cardiacmyocytes apoptosis was reduced significantly in Infarct+PEDF group compared with other groups;the opposite result occurred in Infarct+siPEDF group(P <0.05).Conclusions PEDF can improve ischemic cardiac function through reducing local inflammation and protecting cardiac myocytes.更多还原