GM-CSF及其动员的骨髓源性细胞在创伤愈合中的作用研究

Role of GM-CSF and Mobilized Bone Marrow-derived Cells in Wound Healing

目的研究粒细胞巨噬细胞集落刺激因子(granulocyte macrophage colony-stimulating factor,GM-CSF)及其动员的骨髓源性细胞促进创伤愈合的作用途径。方法采用正常小鼠及化疗、放疗引起的骨髓抑制小鼠模型,背部形成创面,分别给予皮下注射高、低剂量(50,17μg·kg^(-1)) GM-CSF,测量创伤愈合程度;采用MTT观察不同浓度下猪髋动脉内皮细胞(pig iliac endothelium cells,PIECs)增殖状况;采用Matrigel基质胶培养人脐静脉内皮细胞和小鼠动脉环,并给予100 ng·mL^(-1) GM-CSF,观察其微管结构形成情况。结果在小鼠创伤愈合模型中,高剂量GM-CSF(50μg·kg^(-1))组创面修复较低剂量更为明显;在小鼠骨髓抑制模型中,低剂量GM-CSF促进骨髓抑制小鼠的创伤愈合;GM-CSF在0.01～781.25 ng·mL^(-1)明显促进PIECs的增殖;GM-CSF 100 ng·mL^(-1)明显促进人脐静脉内皮细胞和动脉环周围微管形成。结论 GM-CSF通过动员骨髓源性细胞和作用于内皮细胞促进创伤愈合。

OBJECTIVE To investigate the role of GM-CSF and its mobilized bone marrow-derived cells in promoting wound healing. METHODS The myelosuppressive mice model induced by chemotherapy and radiotherapy was established.The wounds were formed on the back and subcutaneously injected with 50, 17 μg·kg-1 GM-CSF to measure the degree of wound healing. MTT was used to observe the proliferation of PIECs. The cultured human umbilical vein endothelial cells and mouse arteries were cultured with mateigel, and 100 ng·mL-1 GM-CSF was administered to observe the formation of microtubules.RESULTS In the mouse wound healing model, wound repair of GM-CSF(50 μg·kg-1) was more obvious than GM-CSF(17 μg·kg-1). A low dose of GM-CSF(17 μg·kg-1) promoted wound healing in myelosuppressed mice. GM-CSF at 0.01-781.25 ng·mL-1 significantly promoted the proliferation of PIECs. GM-CSF 100 ng·mL-1 significantly promoted the formation of microtubules around human umbilical vein endothelial cells and arterial rings. CONCLUSION GM-CSF promotes wound healing by mobilizing bone marrow-derived cells and acting on endothelial cells.