Shao Zhan-Qiang, Takaji Kentaro, Katayama Yukihiro, Kunitomo Ryuji, Sakaguchi Hisashi, Lai Zhong-Fang, Kawasuji Michio
Department of Cardiovascular Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo, Japan.
Circ J. 2006 Apr;70(4):471-7. doi: 10.1253/circj.70.471.
Basic fibroblast growth factor (bFGF) stimulates neoangiogenesis. Incorporation into biodegradable gelatin hydrogels provides the sustained release of bFGF. The effects of intramyocardial injections of slow-release bFGF on neoangiogenesis in a rat model of infarction were investigated.
Myocardial infarction was induced in rats using coronary artery ligation. A total of 124 rats received an intramyocardial injection of 20 microg of bFGF, the same amount of bFGF incorporated into gelatin hydrogel (bFGF + gel), gelatin hydrogel (gel) or saline. Ventricular function was evaluated by echocardiography 2 or 4 weeks later. Morphometric and histological analyses were used to evaluate infarct size, vascular density and myocardial apoptosis. Capillary density in the infarct border zone was higher in the bFGF and bFGF + gel groups than in the saline and gel groups at 4 weeks (p<0.001). Arteriolar density was higher in the bFGF + gel group than in the other 3 groups (p<0.05). The bFGF and bFGF + gel groups contained fewer apoptotic cardiomyocytes in the border zone than the saline and gel groups (p<0.01). The bFGF+gel group had thicker (p<0.05) and less expanded infarcts (p<0.01) compared with the saline group at 4 weeks.
Incorporation of bFGF in gelatin hydrogels enhanced the effects of bFGF on arteriogenesis, ventricular remodeling and cardiac function.
碱性成纤维细胞生长因子(bFGF)可刺激新生血管形成。将其掺入可生物降解的明胶水凝胶中可实现bFGF的持续释放。本研究探讨了心肌内注射缓释bFGF对大鼠梗死模型新生血管形成的影响。
采用冠状动脉结扎法诱导大鼠心肌梗死。124只大鼠接受心肌内注射20微克bFGF、等量掺入明胶水凝胶的bFGF(bFGF+凝胶)、明胶水凝胶(凝胶)或生理盐水。2周或4周后通过超声心动图评估心室功能。采用形态计量学和组织学分析评估梗死面积、血管密度和心肌细胞凋亡情况。4周时,bFGF组和bFGF+凝胶组梗死边缘区的毛细血管密度高于生理盐水组和凝胶组(p<0.001)。bFGF+凝胶组的小动脉密度高于其他3组(p<0.05)。bFGF组和bFGF+凝胶组梗死边缘区的凋亡心肌细胞少于生理盐水组和凝胶组(p<0.01)。与生理盐水组相比,4周时bFGF+凝胶组的梗死灶更厚(p<0.05)且扩张程度更小(p<0.01)。
将bFGF掺入明胶水凝胶中可增强bFGF对动脉生成、心室重塑和心脏功能的作用。