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在正常和后肢缺血模型中使用重组碱性成纤维细胞生长因子与去端肽胶原进行血管生成研究。

Angiogenesis Using Recombinant Basic Fibroblast Growth Factor With Atelocollagen in Normal and Hind Limb Ischemia Models.

作者信息

Kotani Atsushi, Watanabe Shin, Kato Takao, Kikuchi Takayuki, Toya Keiji, Hori Katsuhiko, Minobe Noriko, Musumi Kaori, Kimura Yasuko, Nagai Yoji, Yoshimura Jun, Kawamata Hirofumi, Yanishi Kenji, Matoba Satoaki

机构信息

FEF Pharmaceutical Co., Ltd. Tokyo Japan.

Research Center, EPS Innovative Medicine Co., Ltd. Tokyo Japan.

出版信息

Circ Rep. 2025 Mar 15;7(5):372-378. doi: 10.1253/circrep.CR-25-0011. eCollection 2025 May 9.

DOI:10.1253/circrep.CR-25-0011
PMID:40352133
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12061500/
Abstract

BACKGROUND

Basic fibroblast growth factor (bFGF) is an angiogenic factor with a short half-life. Because recombinant bFGF is in clinical use, we hypothesized that the localization of recombinant bFGF with atelocollagen would have angiogenic effects at the injection site in normal and hind limb ischemic animal models.

METHODS AND RESULTS

We administered the recombinant bFGF with atelocollagen intramuscularly to hind limbs in normal rabbits or in a mouse model of femoral artery ligation to explore the pharmacological action for ischemia. We evaluated blood flow in the ischemic/normal limb using laser speckle perfusion imaging and the density of blood vessels by pathological examination. At the administration site in normal rabbits, a significant increase in the number of blood vessels was noted at 14 days post-administration of recombinant bFGF with atelocollagen compared with saline or atelocollagen alone. In mice with femoral artery ligation, blood flow and vessels in the ischemic hind limb increased at 2 weeks after injection and more at 4 weeks after injection, and the effect was most significant in mice administered 100 μg of recombinant bFGF with 3% of atelocollagen.

CONCLUSIONS

Intramuscular administration of recombinant bFGF with atelocollagen induced angiogenesis between 2 and 4 weeks in both normal and ischemic hind limbs.

摘要

背景

碱性成纤维细胞生长因子(bFGF)是一种半衰期较短的血管生成因子。由于重组bFGF已在临床应用,我们推测重组bFGF与去端胶原蛋白的定位在正常和后肢缺血动物模型的注射部位会产生血管生成作用。

方法与结果

我们将重组bFGF与去端胶原蛋白肌肉注射到正常兔的后肢或股动脉结扎小鼠模型中,以探索其对缺血的药理作用。我们使用激光散斑灌注成像评估缺血/正常肢体的血流,并通过病理检查评估血管密度。在正常兔的给药部位,与单独注射生理盐水或去端胶原蛋白相比,在注射重组bFGF与去端胶原蛋白后14天,血管数量显著增加。在股动脉结扎的小鼠中,缺血后肢的血流和血管在注射后2周增加,在注射后4周增加更多,并且在给予100μg重组bFGF与3%去端胶原蛋白的小鼠中效果最显著。

结论

肌肉注射重组bFGF与去端胶原蛋白在正常和缺血后肢均可在2至4周内诱导血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/ebc326eb6635/circrep-7-372-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/4f55838cc109/circrep-7-372-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/bc08a4eefa03/circrep-7-372-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/731a63f09ebe/circrep-7-372-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/ebc326eb6635/circrep-7-372-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/4f55838cc109/circrep-7-372-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/bc08a4eefa03/circrep-7-372-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/731a63f09ebe/circrep-7-372-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2f/12061500/ebc326eb6635/circrep-7-372-g004.jpg

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本文引用的文献

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Circ J. 2018 Dec 25;83(1):217-223. doi: 10.1253/circj.CJ-18-0815. Epub 2018 Nov 9.
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Autologous Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood CD34 Positive Cell Transplantation for Hemodialysis Patients with Critical Limb Ischemia: A Prospective Phase II Clinical Trial.自体粒细胞集落刺激因子动员的外周血 CD34 阳性细胞移植治疗血液透析合并严重肢体缺血患者:一项前瞻性 II 期临床试验。
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