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通过掺入碱性成纤维细胞生长因子的明胶水凝胶增强兔动脉瘤中的纤维化形成。

Enhanced formation of fibrosis in a rabbit aneurysm by gelatin hydrogel incorporating basic fibroblast growth factor.

作者信息

Hong L, Miyamoto S, Yamada K, Hashimoto N, Tabata Y

机构信息

Department of Neurosurgery, Graduate School of Medicine, Kyoto University, 43 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

出版信息

Neurosurgery. 2001 Oct;49(4):954-60; discussion 960-1. doi: 10.1097/00006123-200110000-00030.

DOI:10.1097/00006123-200110000-00030
PMID:11564258
Abstract

OBJECTIVE

This study was undertaken to analyze whether the controlled release of basic fibroblast growth factor (bFGF) can promote intrasaccular thrombosis in an experimental aneurysmal model.

METHODS

Carotid aneurysms were constructed in 80 rabbits with venous pouches and treated by placing gelatin hydrogels into each aneurysm incorporating 0, 25, 50, or 100 microg of bFGF or incorporating 100 microg of bFGF with different water contents. In the controls, the venous pouches either were not treated or were treated with gauze alone. Gelatin hydrogel was used for the controlled release of bFGF into the aneurysms. The formation of fibrosis in the aneurysms was histologically viewed to assess the area occupied by the fibrous tissues at 3 and 6 weeks after the hydrogel application. The effect of the bFGF dose and water content on obliterating the aneurysm by the hydrogels incorporating bFGF was also investigated.

RESULTS

Six weeks after the application of gelatin hydrogels with a water content of 95 wt% incorporating 100 microg of bFGF, the lateral pouch orifice was completely closed, obliterating the aneurysm at the level of tissue appearance, in contrast to hydrogels incorporating lower doses of bFGF and other control agents. The venous pouch aneurysm was histologically occupied with the newly formed fibrous tissue, and the fibrous tissue area and percentage of the aneurysmal lumen occupied by the fibrosis-gauze complex were significantly larger than those of other hydrogel applications (P < 0.05). The neointima tissue was homogeneously covered with a monolayer of Factor VIII-positive cells. The fact that there was no difference in the water content in the fibrosis formation induced by the bFGF-incorporated gelatin hydrogels indicated that the hydrogel biodegradability did not affect the obliteration of the aneurysm.

CONCLUSION

Local controlled release of bFGF stimulated the formation of in vivo fibrosis, resulting in obliteration of the aneurysm. The long-term results of the fibrous organization remain speculative.

摘要

目的

本研究旨在分析碱性成纤维细胞生长因子(bFGF)的控释是否能促进实验性动脉瘤模型的瘤内血栓形成。

方法

用静脉袋在80只兔中构建颈动脉动脉瘤,并通过向每个动脉瘤内植入含0、25、50或100微克bFGF的明胶水凝胶或含不同含水量的100微克bFGF的明胶水凝胶进行治疗。在对照组中,静脉袋要么不治疗,要么仅用纱布治疗。明胶水凝胶用于将bFGF控释到动脉瘤中。通过组织学观察动脉瘤内纤维化的形成,以评估水凝胶应用后3周和6周时纤维组织所占面积。还研究了bFGF剂量和含水量对含bFGF水凝胶闭塞动脉瘤的影响。

结果

与含较低剂量bFGF的水凝胶和其他对照剂相比,在植入含100微克bFGF且含水量为95 wt%的明胶水凝胶6周后,外侧袋口完全闭合,在组织外观水平上使动脉瘤闭塞。静脉袋动脉瘤在组织学上被新形成的纤维组织占据,纤维化-纱布复合物所占的纤维组织面积和动脉瘤腔百分比显著大于其他水凝胶应用组(P<0.05)。新生内膜组织均匀地覆盖有单层VIII因子阳性细胞。含bFGF的明胶水凝胶诱导的纤维化形成中含水量无差异,这表明水凝胶的生物降解性不影响动脉瘤的闭塞。

结论

bFGF的局部控释刺激了体内纤维化的形成,导致动脉瘤闭塞。纤维组织的长期结果仍有待推测。

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