Combined Use of Acid Fibroblast Growth Factor, Granulocyte Colony-stimulating Factor and Zinc Sulphate Accelerates Diabetic Ulcer Healing

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概要

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• Our previous studies demonstrated that topic application of recombinant human acid fibroblast growth factor (aFGF) significantly, but still not completely, improved in diabetic ulcer healing. To obtain a maximal therapy for diabetic ulcer healing, a combined protocol containing aFGF, anti-oxidative reagent zinc (Zn) and stem cell stimulator granulocyte colony-stimulating factor (G-CSF), i.e.: aFGF/G-CSF/zinc sulphate (ZnSO4), was explored in the present study. Diabetes was induced by a single dose of streptozotocin (STZ, 55 mg/kg) in Sprague Dawley rats, and full thickness skin wound was made in diabetic rats at 2 months after diabetes onset. Diabetic ulcer rats were treated with aFGF, G-CSF, ZnSO4, aFGF/G-CSF/ZnSO4 or vehicle control, respectively and 3, 6, 9, 12, 15, 18, 21 and 28 days later, therapeutic effects were evaluated by calculating ulcer area. On day 7, 14, 21 after treatment, rats were sacrificed to collect 2 pieces of dorsal skin from 3 different sites (wound center, edge and healed area) to perform histopathological examination. Results showed that treatment with aFGF/G-CSF/ZnSO4 significantly enhanced ulcer healing compared with single drug treatment groups at different time points. Healing times for 100% of the wound in the aFGF/G-CSF/ZnSO4 group was 20.00±1.15 days, and significantly shorter than those in single treatment groups (p<0.05). Histopathological and immunohistochemical analysis disclosed significant increases in capillary density, proliferating cells, the expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and the ratios of TIMP-1 to matrix metalloproteinase 1 (MMP-1) in aFGF/G-CSF/ZnSO4 group as compared to other single treatments. Collectively, the combinative protocol of aFGF/G-CSF/ZnSO4 significantly enhanced the therapeutic effect on diabetic ulcer wound, probably through the promotion of fibroblast proliferation and differentiation, enhancement of blood vessel regeneration, and up-regulation of TIMP-1 and down-regulation of MMP-1 expression in diabetic ulcer healing process.

著者

• Cai Lu

  The Chinese-american Res. Inst. For Diabetic Complications

• Xiao Jian

  Institute Of Tissue Transplantation And Immunology Jinan University

• Lin Shaoqiang

  School Of Pharmaceutical Science Wenzhou Medical College

• Jia Xinglong

  Institute Of Tissue Transplantation And Immunology Jinan University

• Lin Shaoqiang

  The Chinese-American Research Institute for Diabetic Complications

• Xu Hengwu

  The Chinese-American Research Institute for Diabetic Complications

• Xiao Jian

  The Chinese-American Research Institute for Diabetic Complications

• Liu Yanlong

  The Chinese-American Research Institute for Diabetic Complications

• Zhang Yi

  The Chinese-American Research Institute for Diabetic Complications

• Li Xiaokun

  The Chinese-American Research Institute for Diabetic Complications

• Tan Yi

  The Chinese-American Research Institute for Diabetic Complications

• Cai Lu

  The Chinese-American Research Institute for Diabetic Complications

関連論文

• Cardiac Protection by Basic Fibroblast Growth Factor from Ischemia/Reperfusion-Induced Injury in Diabetic Rats
• Combined Use of Acid Fibroblast Growth Factor, Granulocyte Colony-stimulating Factor and Zinc Sulphate Accelerates Diabetic Ulcer Healing
• Mechanism of antitumor effect of a novel bFGF binding peptide on human colon cancer cells
• Comparison of the Therapeutic Effects Recombinant Human Acidic and Basic Fibroblast Growth Factors in Wound Healing in Diabetic Patients
• Cardiac Functional Analysis by Electrocardiography, Echocardiography and in situ Hemodynamics in Streptozotocin-Induced Diabetic Mice

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