在体评价SDF-1靶向微泡在AMI干细胞移植中的作用

At present stem cell transplantation become a promising treatment for myocardial infarction, but,the result of transplantation is affected by various factors:stem cells and micro environment. A lot of research found that SDF-1 is main index in transplant area which reflect the quality of environment of transplant area. SDF-1 / CXCR4 plays an important role in myocardial injuries repair and in stem cell migration、 survive and differentiation for function cells. And the expression level of SDF-1 is different in different period after myocardial infarction. But at present, the SDF-1 is detected mainly in vitro through immunohistochemical and molecular biology examination and evaluated hardly in vivo. Therefore, how to apply noninvasive technique to evaluate the SDF-1 is a difficult problem to be solved in clinical. To establish acute myocardial infarction reperfusion model of pig and make targeted contrast agents through directly connected SDF-1 antibody and microbubble，this study,in vivo, target recognize and quantitative evaluate the SDF-1 in myocardial infarction area through intravenous injection of targeted contrast agents，at the same time，transplant stem cell. The final purpose of this study offers an in vivo and noninvasive new molecular imaging methods for evaluation of stem cell transplantation micro environmental and optimum time window and patient of stem cell transplantation.

目前干细胞移植已成为心肌梗死后极具前景的治疗方法，然而，移植效果受到干细胞和微环境两方面的影响。大量研究证实SDF-1是移植区微环境的重要组成部分，SDF-1与其受体CXCR4结合后在心肌损伤再生修复中发挥着重要作用，对干细胞的动员、迁移、增殖、存活和分化均有促进作用,并且SDF-1在心肌梗死后不同时间段的表达水平不同。但目前移植区SDF-1含量的检测主要是通过处死动物后取标本行离体检查，难以用于临床的在体评价。因此，如何应用无创技术实现SDF-1检测的在体评价，是临床目前亟待解决的难点问题。本研究通过建立猪急性心肌梗死后再灌注模型，将携带了SDF-1抗体的靶向微泡通过周围静脉注射，对心肌梗死干细胞移植区域SDF-1含量进行在体定量评价并找出SDF-1的峰值表达时间，为临床评估干细胞移植区微环境中SDF-1的最佳表达时间窗和术前筛选最佳移植病例提供一种新的分子影像学方法。

背景：干细胞移植已成为心肌梗死后极具前景的治疗方法，而移植效果受到干细胞和微环境两方面的影响，SDF-1是移植区微环境的重要组成部分，如何应用无创技术实现SDF-1的在体评价是目前临床亟待解决的难点问题。方法：本课题将39头中华小型猪随机抽取3头作为对照组，余36头分为6组（根据心肌梗死后不同时间点，1d，3d，1w，2w，3w，4w），每组分成两个亚组：SDF-1测量组（n=3）和干细胞移植组（n=3），SDF-1测量组和对照组均注射携SDF-1单克隆抗体靶向造影剂（T+T组）和普通造影剂（T+C组），获得心肌灌注参数（A、β、A×β），PCR获得SDF-1定量结果。干细胞移植组经冠状动脉注射骨髓干细胞，检测心肌梗死后不同时间点干细胞归巢量。结果：T+T组心肌灌注参数与SDF-1变化趋势一致，于1w达到峰值，A、β、A×β与SDF-1具有相关性（r=0.887，0.892，0.942）, A×β ( X )与SDF-1（Y）建立回归方程Y=0.0945X+0.6685（R2=0.8871）。T+T组心肌灌注参数与干细胞归巢数量于1w均达峰值， A、β、A×β与干细胞归巢数量具有相关性（r=0.658,0.778,0.777），A×β(X)与干细胞归巢数量(Y)建立回归方程Y=50.023+3.348X (R2=0.604)。结论：靶向造影剂心肌灌注参数值可以动态评价干细胞归巢数量时间窗的变化规律，为临床评估干细胞移植区微环境中SDF-1的最佳表达时间窗和术前筛选最佳移植病例提供一种新的分子影像学方法。