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

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。目的：探讨在明胶海绵片(GSS)中加入碱性成纤维细胞生长因子(BFGF)对实验性AAA的影响。实验分为3组：1)未处理组，2)单纯GSS组，3)含100 ng bFGF蛋白的GSS组(bFGF+GSS)。弹性酶注射后，将GSS置于主动脉上方。观察术后14天(POD)的主动脉内径和主动脉破裂率，并于术后14天取材进行病理和转录检测。结果：弹性蛋白酶注射60min后，未治疗对照组的主动脉直径由1.58±0.06 mm显著增大至7.74±1.97 mm。然而，这样的…此外，单纯GSS组和bFGF+GSS组的主动脉增宽均明显减小至4.93~1.38 mm。4.39±0.92 mm。病理结果显示，未经治疗的对照组大鼠的弹力纤维和SMC明显减少，而bFGF+GSS组大鼠的这种减少明显减轻。单独使用GSS的大鼠表现出较少的减少，尽管在单独使用GSS的大鼠和未处理的对照组之间没有统计差异。免疫组织化学染色显示，单纯GSS组和bFGF+GSS组内源性转化生长因子-b和碱性成纤维细胞生长因子阳性细胞增多。碱性成纤维细胞生长因子+GSS组基质金属蛋白酶-9(MMP9)的转录信号较未处理对照组和GSS单独组显著降低。弹性酶注射75分钟后，50%的未经任何治疗的大鼠、38%的单纯GSS组和22%的bFGF+GSS组的大鼠发生了主动脉破裂。结论：我们不仅观察到了弹性酶对实验性AAA进展的治疗作用，而且还观察到了其对GSS的治疗作用。GSS除具有外包裹的动态效应外，还可能通过产生内源性生长因子发挥治疗作用，可能是GSS降解所致。碱性成纤维细胞生长因子可促进SMC的增殖，同时抑制基质金属蛋白酶-9的表达，可能导致弹性纤维的保护，从而降低主动脉破裂的发生率。我们目前的研究表明，这种可能抑制AAA进展的新疗法具有潜在的实用价值。较少

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