In vivo tissue distribution of fibroblast growth factor-1 after intraarterial delivery.

In vivo tissue distribution of fibroblast growth factor-1 after intraarterial delivery.
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动脉内递送后成纤维细胞生长因子-1 的体内组织分布。

DOI:
10.1097/00002480-199507000-00087
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发表时间:
1995
期刊:
ASAIO journal (American Society for Artificial Internal Organs : 1992)
影响因子:
--
通讯作者:
Greisler,HP
Greisler,HP
中科院分区:
--
文献类型:
--
作者:
Hirko,MK;Lin,PH;Gosselin,C;Ren,D;Greisler,HP

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成纤维细胞生长因子-1(成纤维细胞生长因子-1)联合肝素在优化自体静脉和合成血管移植物愈合方面的临床适用性已被提出。作者报道了将成纤维细胞生长因子-1和肝素悬浮液浸渍到扩张的聚四氟乙烯移植物上,促进了内皮细胞的增殖,同时增加了毛细血管形成,并最小限度地减少了内膜增生。本研究对动脉内持续输注的125I-FGF1的组织分布进行了研究。4只新西兰大白兔经左颈动脉近端持续注入125I-成纤维细胞生长因子-1(1.1 ng)和肝素(28U),用Alza公司的渗透压激活泵持续注入24小时。24小时后处死兔子,放血,取肝、肾、脾、肺、心脏、甲状腺、肌肉和脂肪组织。对这些样本进行放射性测定,结果以组织湿重和干重的CPM 125I/g表示。摄取125碘-成纤维细胞生长因子-1(cpm/g干重)甲状腺最大(551.1±131.4)。这比中等摄取的器官(肺、肝、肾、脾和心脏)大2.5-5.5倍(p≤0.0 1)。血液、肌肉和脂肪的摄取量最低。在湿重比较中也发现了类似的分布模式。肝脏中125I-FGF1含量最高,为818.1±176.3 cpm(p≤0.002),其次为肺(204.7±38.5cpm)和肾脏(191.2±11.9cpm)。虽然目前还没有关于成纤维细胞生长因子-1诱导毒性的报道,但这些结果将使在临床试验之前进行进一步的组织特异性毒理学研究成为可能。
The clinical applicability of fibroblast growth factor-1 (FGF-1) plus heparin delivery in optimizing the healing of both autogenous vein and synthetic vascular grafts has been suggested. The authors have reported enhanced endothelial cell proliferation, concurrent increased capillarization, and minimal intimal hyperplasia using suspensions of FGF-1 and heparin impregnated onto expanded polytetrafluoroethylene grafts. The current study characterizes the tissue distribution of 125 I-FGF-1 delivered by continuous intraarterial infusion. 125 I-FGF-1 (1.1 ng) and heparin (28 U) were continuously infused into the thoracic aorta via the proximal end of the ligated left carotid artery for 24 hr in four New Zealand white rabbits using an Alzet (Alza Corp., Palo Alto, CA) osmotically activated pumping device. Rabbits were sacrificed after 24 hr, exsanguinated, and biopsies taken from the liver, kidneys, spleen, lungs, heart, thyroid gland, muscle, and fat. These samples were assayed for radioactivity and results expressed as cpm 125 I/gram of both wet and dry weight of tissue. 125 I-FGF-1 uptake (cpm/g dry wt.) was greatest in the thyroid (551.1±131.4). This was 2.5–5.5× greater (p≤ 0.01) than those organs with intermediate uptake (lungs, liver, kidneys, spleen, and heart). Lowest uptake was noted in the blood, muscle, and fat. A similar distribution pattern was found in wet weight comparisons. Total organ 125 I-FGF-1 content was greatest in the liver at 818.1±176.3 cpm (p≤ 0.002) and intermediate in the lungs (204.7±38.5 cpm) and kidneys (191.2±11.9 cpm). Although no FGF-1-induced toxicity has yet been reported, these results will allow for future tissue-specific toxicology studies before clinical trials.