中国组织工程研究 ›› 2013, Vol. 17 ›› Issue (24): 4473-4480.doi: 10.3969/j.issn.2095-4344.2013.24.015

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

冠状静脉逆行灌注碱性成纤维细胞生长因子的体内浓度梯度

甄 雷1,王 晓1,缪黄泰1,乔世斌1, 2,吴星欣1,乔 岩3,刘百球3,刘新民3,阙 斌1,聂绍平1   

  1. 1首都医科大学附属北京安贞医院急诊危重症中心,北京市心肺血管疾病研究所,北京市  100029
    2山东省日照市人民医院心内一科,山东省日照市  276826
    3首都医科大学附属北京安贞医院心内科,北京市心肺血管疾病研究所,北京市  100029
  • 收稿日期:2013-02-16 修回日期:2013-04-21 出版日期:2013-06-11 发布日期:2013-06-11
  • 通讯作者: 聂绍平,博士,主任医师,教授,博士生导师,首都医科大学附属北京安贞医院急诊危重症中心,北京市心肺血管疾病研究所,北京市100029 spnie@126.com
  • 作者简介:甄雷★,男,1986年生,河北省保定市人,汉族,2013年首都医科大学毕业,硕士,主要从事冠心病基础和临床研究。
  • 基金资助:

    本文受国家自然科学基金面上项目(81070166,81270284)以及北京市教育委员会科技发展计划面上项目(KM201010025020)资助

In vivo concentration gradient of basic fibroblast growth factor after coronary venous retrograde perfusion

Zhen Lei1, Wang Xiao1, Miu Huang-tai1, Qiao Shi-bin1, 2, Wu Xing-xin1, Qiao Yan3, Liu Bai-qiu3, Liu Xin-min3, Que Bin1, Nie Shao-ping1   

  1. 1 Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heat, Lung and Blood Vessel Diseases, Beijing  100029, China
    2 Department of Cardiology, People’s Hospital of Rizhao, Rizhao  276826, Shandong Province, China
    3 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing  100029, China
  • Received:2013-02-16 Revised:2013-04-21 Online:2013-06-11 Published:2013-06-11
  • Contact: Nie Shao-ping, M.D., Chief physician, Doctoral supervisor, Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heat, Lung and Blood Vessel Diseases, Beijing 100029, China spnie@126.com
  • About author:Zhen Lei★, Master, Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heat, Lung and Blood Vessel Diseases, Beijing 100029, China
  • Supported by:

    General Program of National Natural Science Foundation of China, No. 81070166*, 81270284*; General Program of Science and Technology Planning of Beijing Municipal Education Commission, No. KM201010025020*

摘要:

背景:体外研究发现,碱性成纤维细胞生长因子浓度梯度能够促进干细胞的迁移和增殖。然而,采用冠状静脉逆行灌注途径能否建立在体碱性成纤维细胞生长因子浓度梯度尚不明确。
目的:评价冠状静脉逆行灌注实验方法的安全性,建立并检测冠状静脉与局部缺血心肌间的碱性成纤维细胞生长因子浓度梯度,探讨逆行灌注后碱性成纤维细胞生长因子浓度梯度存在的时间窗。
方法:开胸结扎法建立犬急性心肌梗死模型,1周后经冠状静脉逆行灌注碱性成纤维细胞生长因子。灌注结束后球囊充盈时间分别为0,5,10,15 min。解除球囊充盈后即刻处死动物,ELISA法测量血浆和梗死区心肌、梗死边缘区心肌组织匀浆中碱性成纤维细胞生长因子的浓度,在体评价在不同时间点冠状静脉血液与梗死区心肌以及梗死边缘区心肌之间的碱性成纤维细胞生长因子浓度梯度。
结果与结论:逆行灌注成功率为100%,无死亡、心脏压塞和恶性心律失常等并发症发生。灌注后5 min和10 min,冠状静脉血液与梗死区心肌之间碱性成纤维细胞生长因子浓度的差异有显著性意义,梗死区心肌浓度明显高于其他2种组织。球囊充盈15 min后2组之间浓度差异无显著性意义。结果表明,经冠状静脉逆行灌注碱性成纤维细胞生长因子后,球囊充盈的时间为5-10 min能在冠状静脉血液与梗死心肌之间建立稳定的碱性成纤维细胞生长因子浓度梯度,而且在梗死心肌区域浓度最高。此时间窗内灌注干细胞有望增强其移行活力。

关键词: 组织构建, 组织构建与生物活性因子, 缺血性心脏病, 冠状静脉逆行灌注, 生长因子, 干细胞, 在体, 浓度梯度, 碱性成纤维细胞生长因子, 骨髓间充质干细胞, 国家自然科学基金

Abstract:

BACKGROUND: In vitro studies have demonstrated that the concentration gradient of basic fibroblast growth factor can promote the migration and proliferation of stem cells. However, it is unclear whether in vivo basic fibroblast growth factor concentration gradient can be established by coronary venous retrograde perfusion.
OBJECTIVE: To evaluate the safety of coronary venous retrograde perfusion and establish the concentration gradient of basic fibroblast growth factor between coronary venous blood and target myocardium, and to investigate the time window of basic fibroblast growth factor concentration gradient after coronary venous retrograde perfusion.
METHODS: The acute myocardial infarction models were established with ligating method, and 1 week later, coronary venous retrograde perfusion of basic fibroblast growth factor was performed. After perfusion, the time of balloon dilation was 0, 5, 10 and 15 minutes. The animals were sacrificed immediately after balloon inflation lifting, and then the enzyme-linked immunosorbent assay was used to measure the concentration of basic fibroblast growth factor in the plasma, farcted myocardium and homogenates of myocardium in the infarct border zone. The basic fibroblast growth factor concentration gradient between the coronary venous blood and infarcted myocardium and myocardium in the infarct border zone was in vivo evaluated.  
RESULTS AND CONCLUSION: The success rate of coronary venous retrograde perfusion was 100%. No death, cardiac tamponade, or ventricular arrthythmia occurred. There was no significant difference in concentration of basic fibroblast growth factor between coronary venous blood and infarcted myocardium at 5 and 10 minutes after perfusion, while the concentration of basic fibroblast growth factor in the infarcted myocardium was higher than that in the coronary venous blood and myocardium in the infarct border zone. There was no significant difference in the concentration between two groups after balloon dilation for 15 minutes. The results indicate that after coronary venous retrograde perfusion of basic fibroblast growth factor, the time of balloon dilation was 5-10 minutes which can establish stable basic fibroblast growth factor concentration gradient between the coronary venous blood and infarcted myocardium, and the concentration is highest in the infarcted myocardium. The stem cell infusion in this time window can enhance its transitional vitality.

Key words: tissue construction, tissue construction and bioactive factors, ischemic heart disease, coronary venous retrograde perfusion, growth factor, stem cells, in vivo, concentration gradient, basic fibroblast growth factor, bone marrow mesenchymal stem cells, National Natural Science Foundation of China

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