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) 促进血管平滑肌细胞 (SMC) 增殖，因此可能抑制腹主动脉瘤 (AAA) 的进展，我们研究了将 bFGF 掺入明胶海绵片中的效果。 (GSS)，它可以延长 bFGF 对实验性 AAA 的作用。方法：在雄性 Sprague-Dawley 大鼠中诱导实验性 AAA根据治疗将大鼠分为三组：1）未处理的对照组，2）单独的GSS，3）将含有100ng bFGF蛋白的GSS（bFGF+GSS）放置在主动脉上。我们评估了术后 14 天 (POD) 的主动脉直径和主动脉的破裂率，并于 14 日收获主动脉。 POD 14 进行病理和转录检查。结果：在未经治疗的对照中，弹性蛋白酶输注 60 分钟显着扩大了主动脉直径，从 1.58 ± 0.06 mm 增至 7.74 ± 1.97 mm，但是，单独使用 GSS 时，这种主动脉的增大显着减少。 bFGF+GSS 为 4.93 1.38 毫米和。病理学结果分别显示，未经治疗的对照组的弹性纤维和 SMC 显着减少，而使用 bFGF+GSS 的大鼠则显着减弱了这种减少，而单独使用 GSS 的大鼠则显示出较少的减少，尽管没有。单独使用 GSS 的大鼠和未处理的对照大鼠之间存在统计学差异，免疫染色显示单独的 GSS 和 bFGF+GSS 中内源性 TGFβ 和 bFGF 的阳性细胞有所增加。与未经治疗的对照组或单独注射 GSS 75 分钟相比，bFGF+GSS 中的基质金属蛋白酶-9 (MMP-9) 显着降低，在未进行任何治疗的情况下，50% 的大鼠发生主动脉破裂，而对照组中 38% 的大鼠发生主动脉破裂。单独患有 GSS 的大鼠，以及 22% 患有 bFGF+GSS 的大鼠。结论：我们不仅注意到 bFGF+GSS 对实验性 AAA 进展的治疗效果，单独的 GSS 也可能通过 GSS 降解诱导内源性生长因子的产生产生治疗作用，此外，bFGF 的动态作用可能会增殖 SMC，同时抑制 MMP-9 的表达可能导致。保留弹性纤维，这可能会降低主动脉破裂的发生率，这表明这种新疗法的潜在用途可能会抑制 AAA 的进展。