静脉应用血小板源性生长因子质粒减小梗死心肌面积的可行性  

Feasibility of reducing myocardial infarct area using intravenous injection of platelet-derived growth factor plasmid

作　　者：王健[1,2,3] 姚瑶[1,2,3] 李丹[1,2,3] 沈晓涛[1,2,3,4] 郑馨[1,2,3] 刘少坤[1,2,3] 刘娟娟[1,2,3] 蔡冬青[1,2,3,4] 

机构地区：[1]暨南大学再生医学教育部重点实验室,广东省广州市510632 [2]暨南大学再生医学香港中文大学一暨南大学联合实验室,广东省广州市510632 [3]暨南大学广东省科技厅国际科技合作基地,广东省广州市510632 [4]暨南大学生物医学工程系,广东省广州市510632

出　　处：《中国组织工程研究与临床康复》2010年第20期3669-3673,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：863项目(2007AA02Z105);国家自然科学基金(30770886,30570369,30340038,30973158);广东省自然科学基金重点项目(04105826);广东省科技攻关项目(2004B30601007);教育部留学回国人员基金;广州市科技攻关项目(2006Z3-E5251)的资助~~

摘　　要：背景:过往研究已证实:心肌缺血前或缺血时心肌内注射血小板源性生长因子及其基因载体均可以明显减小缺血心肌的梗死面积,但心肌梗死后才经静脉使用血小板源性生长因子的基因载体是否具有相同的疗效,所知甚少。目的:进一步验证对心肌缺血后,经静脉注射血小板源性生长因子质粒phPDGF-B对缺血心肌梗死面积的作用。方法:20只SD大鼠随机分为4组,经结扎左冠状动脉前降支,建立心肌梗死模型。于结扎后30min,雌、雄实验组静脉注射phPDGF-B质粒;雌、雄对照组静脉注射等体积PBS。2周后,进行常规的Masson,s Trichrome染色,对缺血心肌梗死区面积、纤维化及心室几何参数进行分析。结果与结论:大鼠静脉使用phPDGF-B质粒2周后,雌、雄实验组的心肌梗死的面积均明显小于雌、雄对照组(P<0.05);实验组梗死区存活的心肌细胞明显多于对照组;雌、雄实验组梗死区纤维化面积的比值均低于对照组,但差异没有显著性意义;实验组梗死区胶原沉积的密度明显小于对照组;实验组梗死边缘区的室壁厚度大于对照组(P<0.05)。实验组梗死区室壁厚度大于对照组。结果证实,在心肌缺血30min,经静脉使用phPDGF-B质粒对梗死区心肌细胞存活有保护作用,能有效减小缺血心肌的坏死面积,同时能有限度地改善存在心肌梗死的左心室重构,以及减小梗死区的纤维化程度,且上述作用没有性别差异。BACKGROUND： Previous studies have demonstrated that intramyocardial injection of platelet-derived growth factor （PDGF） and its encoded gene vector prior to or immediately after myocardial ischemia is able to decrease myocardial infarcted areas. However, whether intravenous injection of PDGF gene vector after myocardial infarction has the same effect is still unclear. OBJECTIVE： To investigate the effect of intravenous injection of phPDGF-B plasmid on infarct areas after myocardial infarction. METHODS： Twenty Sprague Dawley rats were prepared for myocardial infarction models and randomly divided into 4 groups. The phPDGF-B plasmid was intravenously injected into the male and female experimental groups at 30 minutes after ligation. In the male, female control groups, the same volume of phosphate buffered saline was injected. The Masson Trichrome staining was performed at 2 weeks after operation, and the infarcted area, the infarcted zone fibrosis and the geometry of left ventricle were analyzed. RESULTS AND CONCLUSION： The infarcted areas of the experimental groups were less than that of the control groups at 2 weeks after injection （P 0.05）. Compared with the control groups, a lot of viable cells were found in infarcted zone in the experimental groups. Even though, the area of the fibrosis in the experimental groups was less than control groups, however, the difference had no statistical significance. In addition, the collagen deposition density in the experimental groups was less than control groups. Furthermore, it was found that the wall thickness of border zone in left ventricle of experimental groups was longer than control groups （P 0.05）; while the thickness of infarcted myocardium in left ventricle was greater than that of the control group. All results demonstrated that intravenous delivery of phPDGF-B plasmid had a protective effect on the myocytes of infarcted area, which can decrease the infarction size of ischemic myocardium, improve the reconstruction of left ventricle geometry an

关 键 词：血管新生 心肌梗死 PDGF-BB质粒 左心室重构 静脉给药 大鼠 

分 类 号：R318[医药卫生—生物医学工程]