缓释降解支架复合碱性成纤维细胞生长因子诱导心肌血管再生的作用(英文)

Degradable scaffolds combined with basic fibroblast growth factor for myocardial angiogenesis

背景:研究证实碱性成纤维细胞生长因子具有刺激血管再生及侧支重建的作用,但是,以往多通过外周静脉、左心房或冠脉介入途径给药,心肌局部难以达到有效治疗浓度。目的:基于高分子材料聚乳酸/乙醇酸的降解特性,复合碱性成纤维细胞生长因子,保证蛋白生长因子在局部组织中靶向释放,观察其诱导心肌血管再生效果。方法:以聚乳酸、乙醇酸为原料,二氯甲烷溶解后加入重组人碱性成纤维细胞生长因子,通过模具塑形,制成外径/内径分别为3.0/2.8mm、壁厚0.1mm、长度10mm的圆柱形中空管状支架备用。于小型猪冠脉前降支中、远端1/3交界处阻断,局部心肌颜色变为暗紫色,超声观察前壁心尖局部室壁运动异常证实模型制作成功,随机分至空白支架对照组和碱性成纤维细胞生长因子支架组,支架通过自主设计的机械打孔装置植入。6周后,免疫组织化学染色量化分析血管重建的增殖细胞数量,并结合Image Pro Plus软件量化各组新生血管密度,SPECT结合软件Emory Cardiac Toolbox分析灌注缺损区域质量百分率的变化。结果与结论:6周后碱性成纤维细胞生长因子支架组增殖细胞数量、新生血管密度较空白支架组显著增加(P<0.001),心肌核素显像显示灌注质量缺损百分率较空白支架组显著减少(P<0.001)。结果证实,复合碱性成纤维细胞生长因子的聚乳酸/乙醇酸支架能够显著增加新生血管密度,进而改善缺血部位心肌血流灌注。

BACKGROUND：Studies have shown that basic fibroblast growth factor has effects on stimulating vessel regeneration and collateral reconstruction.However,administration was performed mostly by peripheral vein,left atrium or percutaneous coronary intervention,and it is difficult to achieve an effective therapeutic concentration in the local myocardium.OBJECTIVE：Based on the property of poly（D,l-lactic-coglycolic acid）（PLGA）,to investigate outcomes of inducing neovascularization in the myocardium in combination of basic fibroblast growth factor（bFGF） by ensuring target release of protein growth factor in local tissue.METHODS：PLGA and bFGF were dissolved in dichloromethane.This liquid mixture was rolled into the form of a hollow tube（3.0 mm outer diameter,2.8 mm inner diameter,0.1 mm thick,10 mm length） for further use.The middle third of the left anterior descending coronary artery of mini-swines was ligated,and the local myocardium became dark purple.After the successful establishment by abnormal regional wall motion in the cardiac apex at anterior wall using ultrasound,the mini-swines were assigned to channels and bare scaffolds（BS） group and channels and bFGF-incorporating scaffolds（FS） group.The scaffold was implanted in the myocardium using self-made hollow bit.At 6 weeks,the number of proliferative cells was quantified by immunohistochemical staining.New vessels were quantified utilizing Image-Pro Plus software package in both groups.Quantitative analysis of changes in mass defect percentage was performed by Emory Cardiac Toolbox software combined with single-photon-emission computed tomography.RESULTS AND CONCLUSION：At 6 weeks,number of proliferative cells and the density of new vessels were significantly increased in the FS group compared with BS group（P 0.001）.Single-photon-emission computed tomography illustrates that MDP was significantly lower in the FS group compared with the BS group（P 0.001）.Results have suggested that PLGA scaffolds that incorporate bFGF were able to induce angiogenesis and enhance blood-flow perfusion.