中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (20): 3669-3673.doi: 10.3969/j.issn.1673-8225.2010.20.014

• 组织构建与生物活性因子 tissue construction and bioactive factors • 上一篇    下一篇

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

王 健123,姚 瑶123,李 丹123,沈晓涛1234,郑 馨123,刘少坤123,刘娟娟123,蔡冬青1234   

  1. 暨南大学,1再生医学教育部重点实验室,2再生医学香港中文大学-暨南大学联合实验室,3广东省科技厅国际科技合作基地,4生物医学工程系,广东省广州市  510632
  • 出版日期:2010-05-14 发布日期:2010-05-14
  • 通讯作者: 蔡冬青,博士,教授,博士生导师,暨南大学再生医学教育部重点实验室,再生医学香港中文大学-暨南大学联合实验室,广东省科技厅国际科技合作基地,生物医学工程系,广东省广州市 510632 tdongbme@jnu.edu.cn
  • 作者简介:王 健,男,1985年生,山西省潞城市人,汉族,暨南大学生命科学技术学院在读硕士,主要从事缺血心肌再生方面的研究。 wangjian6796298@163.com
  • 基金资助:

    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和广州市科技攻关项目(2006Z3-E5251)

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

Wang Jian1,2,3, Yao Yao1,2,3, Li Dan1,2,3, Shen Xiao-tao1,2,3,4, Zheng Xin1,2,3, Liu Shao-kun1,2,3, Liu Juan-juan1,2,3, Cai Dong-qing1,2,3,4   

  1. 1Key Laboratory for Regenerative Medicine, Ministry of Education, 2Joint Laboratory for Regenerative Medicine, the Chinese University of Hong Kong-Jinan University, 3the International Science & Technology Cooperation Base, Guangdong Provincial Department of Science and Technology, 4Department of Biomedical Engineering, Jinan University, Guangzhou  510632, Guangdong Province, China
  • Online:2010-05-14 Published:2010-05-14
  • Contact: Cai Dong-qing, Doctor, Professor, Doctoral supervisor, Key Laboratory for Regenerative Medicine, Ministry of Education, Joint Laboratory for Regenerative Medicine, the Chinese University of Hong Kong-Jinan University, the International Science & Technology Cooperation Base, Guangdong Provincial Department of Science and Technology, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, Guangdong Province, China tdongbme@jnu.edu.cn
  • About author:Wang Jian, Studying for master’s degree, Key Laboratory for Regenerative Medicine, Ministry of Education, Joint Laboratory for Regenerative Medicine, the Chinese University of Hong Kong-Jinan University, the International Science & Technology Cooperation Base, Guangdong Provincial Department of Science and Technology, Jinan University, Guangzhou 510632, Guangdong Province, China wangjian6796298@163.com
  • Supported by:

    the 863 Program, No. 2007AA02Z105*;
    the National Natural Science Foundation of China, No. 30770886*, 30570369*, 30340038*, 30973158*;
    Guangdong Key Grant for Natural Science Foundation, No. 04105826*;
    Guangdong Grant for Science and Technology Development, No. 2004B30601007*;
    Foundation for the Chinese Scholars Returned from Oversea, Ministry of Education and Guangzhou Grant for Science and Technology Development, No. 2006Z3-E5251*

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30 min,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30 min,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。

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

Abstract:

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 and reduce the fibrosis of infarcted area after myocardial infarction. This effect has no difference on different genders

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