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）促进了血管平滑肌细胞（SMC）的增殖，因此，它可能抑制腹主动脉瘤（AAA）的进展。我们研究了纳入明胶赞助商（GSS）中的BFGF的影响，该材料可能会延长BFGF的影响，对实验AAA.Methods：通过基础运动弹性酶在雄性Sprague-Dawley大鼠中诱导了实验AAA。根据治疗方法将大鼠分为三组：1）未处理的对照，2）单独使用GSS，3）含有100 ng BFGF蛋白（BFGF+GSS）的GSS。弹性酶输注后，将GSS放置在主动脉上。 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 increased the aortic diameter from 1.58 0.06 mm to 7.74 f 1.97 mm in the untreated controls.但是，仅GSS和BFGF+GSS的主动脉的增加显着降低至4.93 1.38 mm。分别为4.39 0.92毫米。病理发现表明，未经处理的对照中弹性纤维和SMC的显着减少，而BFGF+GSS的大鼠大大减少了它们的这种减少。单独使用GSS的大鼠显示出较少的减少，尽管单独使用GSS的大鼠和未处理的对照之间没有发现统计差异。免疫染色显示单独的GSS和BFGF+GSS中内源性TGF B和BFGF的阳性细胞增加。与仅在未处理的对照或GSS中相比，BFGF+GSS的基质金属蛋白酶-9（MMP-9）的转录信号显着降低。弹性酶输注75分钟可在50％的大鼠中诱导主动脉破裂，而无需进行任何治疗，只有38％的大鼠单独使用GSS，而有22％的大鼠患有BFGF+GSS.Conclusion：我们注意到单独的BFGF+GSS中对实验性AAA的治疗作用，而且在GSS中也对AAA进行了效果。除外部包裹的动态效应外，GSS可能通过产生可能因GSS降解而引起的内源性生长因子产生治疗作用。 BFGF可能会扩散SMC，同时抑制MMP-9的表达，从而导致弹性纤维的保护，这可能导致较低的主动脉破裂。我们目前的研究表明，这种新型疗法的潜在有用性可以抑制AAA的进展。较少的