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成骨生长肽的合成及其与粒细胞集落刺激因子之间的协同作用(英文)

Synthesis of Osteogenic Growth Peptide and Its Synergetic Effect with Granulocyte Colony Stimulating Factor

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【作者】 刘智慧邵云潮陈红红施德源陈统一崔大敷

【Author】 LIU Zhi-Hui, SHAO Yun-Chao1, CHEN Hong-Hong2, SHI De-Yuan1, CHEN Tong-Yi1, CUI Da-Fu * ( Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, the Chinese Academy of Sciences, Shanghai 200031; 1Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200030; 2Shanghai Yi Zhong Biological Technique Co., Ltd., Shanghai 201203 )

【机构】 中国科学院上海生命科学研究院生物化学与细胞生物学研究所复旦大学附属中山医院骨科上海益众生物技术有限公司中国科学院上海生命科学研究院生物化学与细胞生物学研究所 上海200031上海200030上海201203上海200031

【摘要】 Fmoc法固相合成成骨生长肽 (sOGP) ,HPLC鉴定纯度大于 98.6 % ,质谱测定 ,分子量 15 2 3.5kD ,与理论分子量相符 ,N端全序列测定结果正确。Balb/c小鼠体内实验证实sOGP与临床使用的人重组粒细胞集落刺激因子 (rhG CSF)之间有明显的协同作用。实验共分两部分 :第一 ,sOGP共给予 13天 ,每天 1次 ,其中在给予sOGP 5天后开始同时给予rhG CSF ;第二 ,同时给予sOGP和rhG CSF ,每天 1次 ,连续 10天 (sOGP ,0 .5nmol/鼠 ;rhG CSF ,2 μg/鼠 )。两组都显示 ,sOGP能显著地协同rhG CSF促进外周血白细胞数和淋巴细胞数增加 ,但对外周血红细胞和血小板数无影响。骨髓有核细胞记数、骨髓涂片、胸骨切片和脾脏切片显示 ,联合给予sOGP及rhG CSF并未造成髓系和淋巴系异常增生。因此 ,sOGP是一种可以增强目前临床上广泛使用的rhG CSF功能的新的因子 ,是一种极有开发前景的新药。

【Abstract】 Osteogenic growth peptide (OGP) has been synthesized through Fmoc solid phase synthesis procedure. The purity of synthetic OGP (sOGP) is over 98.6% identified by HPLC, the amino acid sequence and electro-spray mass spectroscopy are consistent with theoretical values. The synergetic effect of sOGP with recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the hematopoiesis was investigated in normal mice. To assess the synergy of sOGP with rhG-CSF, two schemes were designed. In one scheme rhG-CSF was used at the last 8 days of a 13-day treatment with sOGP, while in the other one both cytokines were given concurrently for 10 days [sOGP, 0.5 nmol/day (mouse); rhG-CSF, 2 μg/day (mouse)]. Both schemes showed that sOGP remarkably synergized with rhG-CSF on increment of white blood cell number and lymphocyte number in peripheral blood without any change of red blood cell and platelet counts. Quantitative differential analysis of bone marrow and histological examination of the spleen and sternum showed that sOGP plus rhG-CSF did not cause abnormal hyperplasia, so sOGP is a very hopeful new drug to improve the effectiveness of clinical used rhG-CSF.

  • 【文献出处】 生物化学与生物物理学报 ,Acta Biochimica Et Biophysica Sinica , 编辑部邮箱 ,2003年02期
  • 【分类号】Q516
  • 【被引频次】6
  • 【下载频次】62
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