重组人酸性成纤维细胞生长因子皮肤用药的长期毒性研究

目的：研究重组人酸性成纤维细胞生长因子（rhaFGF)皮肤用药的长期毒性。方法：对新西兰兔破损皮肤连续给药28d，剂量分别为3600，1800，900U／cm^2,观察rhaFGF用药期间和停药后对动物血液学、血液生化学、组织学等方面的影响。结果：rhaFGF的无毒剂量为900U／cm^2;rhaFGF1800U/cm^2用药可见个别动物出现淋巴结、脾白髓、圆小囊固有层及胸腺滤泡增生；3600U／cm^2用药可见半以上动物淋巴结出现淋巴等器官滤泡增生，偶见大脑血管周围出现少量淋巴细胞浸润，个别动物睾丸生精小管精子细胞数量增加。停药2周，上述病理改变减轻。未观察到rhaFGF的延迟性毒性反应。结论：rhaFGF在有效剂量及大于有效15倍的剂量下皮肤外用是安全的。

Study on Long-term Toxicity of Recombinant Human Acidic Fibroblast Growth Factor in Rabbits

AIM:To investigate the long tern toxicity of recombinant human acidic fibroblast growth factor (rhaFGF) in rabbits.METHOD:The long term toxicity was tested in rabbits by daubed rhaFGF to scathe skin at the dose of 3600,1800,900 U/cm 2 respectively, once daily for 28 successive days. The hematological, blood biochemical, pathological examination and so on were conducted at 28 days after treatment or at 14 days after stopping administration. RESULT:No abnormal hematological, blood biochemical, pathological index were found in the group of 900 U/ cm 2. The hyperplasia of lymph gland, splenic white pulp, lamina propria of roundlet vesicular organ,and thymus follicles could be observed in a few of rabbits in the group of 1800 U/cm 2. In the group of 3600 U/cm 2, the hyperplasia above mentioned was observed in moiety rabbits, lymphocyte infiltration all round the brain blood could be seen occasionally, and the count of seminiferous tubule testis increased in a modicum of rabbits. The pathologic changes above mentioned were lessenod after stopping treatment of two weeks. The postpone toxic reaction of rhaFGF was not observed. CONCLUSION:rhaFGF used by skin administration at the dose of efficacy and at the most 15 fold of effective dose is safe.