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Inhibitory effects of basic fibroblast growth factor incorporated into bioabsorbable polymer sponge sheet on the progression of experimental abdominal aortic aneurysms

生物可吸收聚合物海绵片中掺入碱性成纤维细胞生长因子对实验性腹主动脉瘤进展的抑制作用

基本信息

批准号：
18591402
负责人：
SATO Akira
金额：
$ 2.53万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Objective: Basic fibroblast growth factor (bFGF) promotes the proliferation of vascular smooth muscle cell (SMC), and thus, it may inhibit the progression of an abdominal aortic aneurysm (AAA). We investigated the effects of bFGF incorporated into a gelatin sponge sheet (GSS), which could prolong the effects of bFGF, on an experimental AAA.Methods: Experimental AAAs were induced in male Sprague-Dawley rats by infra-aortic elastase infusion. The rats were divided into three groups according to the treatments: 1) untreated control, 2) GSS alone, 3) GSS containing 100 ng of bFGF protein (bFGF+GSS). GSS was placed over the aorta after elastase infusion. We evaluated the aortic diameter at 14 postoperative days (POD) and the rupture rate of the aorta, and the aorta was harvested at POD 14 for pathological and transcriptional examination.Result: Elastase infusion for 60 minutes markedly enlarged the aortic diameter from 1.58 0.06 mm to 7.74 f 1.97 mm in the untreated controls. However, such … More an enlargement of the aorta significantly decreased in both GSS alone and bFGF+GSS to 4.93 1.38 mm and. 4.39 0.92 mm, respectively. The pathological findings revealed a marked reduction of the elastic fibers and SMCs in the untreated controls, whereas the rats with bFGF+GSS significantly attenuated such a reduction in them. The rats with GSS alone showed less of a reduction, although no statistical difference was noted between the rats with GSS alone and the untreated controls. Immunostaining revealed an increase of positive cells for endogenous TGF b and bFGF in both GSS alone and bFGF+GSS. The transcript signals for matrix metalloproteinase-9 (MMP-9) significantly decreased in bFGF+GSS in comparison to those in untreated control or GSS alone. Elastase infusion for 75 minutes induced an aortic rupture in 50% of the rats without any treatment, in 38% of the rats with GSS alone, and in 22% of the rats with bFGF+GSS.Conclusion: We noted the therapeutic effects on experimental AAA progression not only in bFGF+GSS, but also in GSS alone. GSS may have a therapeutic effect by the production of endogenous growth factors possibly induced by degradation of GSS, besides the dynamic effect of external wrapping. bFGF may proliferate SMCs, while suppressing the expression of MMP-9 possibly leading to a conservation of elastic fibers, which might result in a lower incidence of aortic rupture. Our present study suggests the potential usefulness of this novel therapy which may inhibit the progression of AAA. Less

目的：碱性成纤维细胞生长因子（bFGF）可促进血管平滑肌细胞（SMC）的增殖，从而抑制腹主动脉瘤（AAA）的发展。我们研究了明胶海绵片（GSS）中掺入bFGF对实验性AAAs的影响，以延长bFGF对实验性AAAs的作用。方法：采用主动脉下弹性蛋白酶诱导雄性Sprague-Dawley大鼠实验性AAAs。将大鼠按处理方式分为3组：1)未处理对照组，2)单独使用GSS， 3) GSS中含有100 ng bFGF蛋白（bFGF+GSS）。弹力蛋白酶输注后，将GSS置于主动脉上。我们在术后第14天评估主动脉直径（POD）和主动脉破裂率，并在第14天切除主动脉进行病理和转录检查。结果：弹力酶注射60分钟可使未治疗组主动脉直径由1.58 0.06 mm显著增大至7.74 f 1.97 mm。然而，在单独GSS和bFGF+GSS中，主动脉的扩大明显减少到4.93 1.38 mm和。分别为4.39 0.92 mm。病理结果显示，未经治疗的对照组弹性纤维和SMCs明显减少，而bFGF+GSS的大鼠弹性纤维和SMCs的减少明显减弱。单独使用GSS的大鼠表现出较少的减少，尽管单独使用GSS的大鼠与未治疗的对照组之间没有统计学差异。免疫染色显示，无论是单独使用GSS还是bFGF+GSS，内源性TGF b和bFGF阳性细胞均有所增加。基质金属蛋白酶-9 （matrix metalloproteinase-9, MMP-9）转录信号在bFGF+GSS中与未治疗对照或单独GSS相比显著降低。弹力蛋白酶输注75分钟后，50%的大鼠在没有任何治疗的情况下，38%的大鼠单独使用GSS， 22%的大鼠使用bFGF+GSS。结论：我们不仅注意到bFGF+GSS治疗实验性AAA的疗效，而且还注意到GSS单独治疗实验性AAA的疗效。除了外包装的动态作用外，GSS还可能通过降解诱导内源性生长因子的产生而发挥治疗作用。bFGF可能使SMCs增殖，而抑制MMP-9的表达可能导致弹性纤维的保存，从而降低主动脉破裂的发生率。我们目前的研究表明，这种新疗法的潜在用途可能会抑制AAA的进展