骨髓干细胞动员对动脉粥样硬化破裂斑块的稳定与修复作用

目的研究自体骨髓干细胞动员对兔动脉粥样硬化（AS）破裂斑块的稳定与修复作用。方法用液氮冻伤术创建兔AS破裂斑块模型,动员组注射重组人粒细胞刺激因子（rhG-CSF）动员自体骨髓干细胞,对照组注射等量生理盐水,连续5 d。动员第5天抽血分离获取单个核细胞,BrdU标记后经静脉注入动物体内;分别于动员后3d和4周末抽血,ELISA法检测兔血清MMP-9、hsC-RP及PAI-1水平;动员后4周处死兔,HE染色和Masson三色染色观察斑块病理形态,免疫组化染色观察BrdU在斑块区表达情况。结果动员5 d后,动员组兔外周血有核细胞计数及单核细胞比例明显增高;动员后4周,动员组新生内皮细胞及胶原纤维明显增多,在斑块区发现有BrdU标记的阳性细胞,动员组血清MMP-9、hsC-RP及PAI-1水平明显降低。结论应用rhG-CSF动员自体骨髓干细胞能通过促进血管内皮细胞和胶原纤维再生,降低炎症因子及凝血纤溶因子而稳定与修复AS破裂斑块。

Stabilization and Repair of Disrupted Atherosclerotic Plaques by Mobilization of Bone Marrow Stem Cells

Objective To study the effect of mobilization of bone marrow stem cells on stabilization and repair of atherosclerotic disrupted plaques. Methods Rabbit models of disrupted atherosclerotic plaques were established by cold-induced endothelial injury with liquid nitrogen in the right carotid artery. The rabbits of mobilization group were injected with rhG-CSF t for 5 days to mobilize bone marrow stem cells. On the 5th day after mobilization, the bone marrow stem cells from peripheral blood were labeled with bromodeoxyuridine （BrdU） for 24 hours, then reinjeeted intravenously. The rabbits of control group were injected with normal saline for 5 days. After 4 weeks, the disrupted atheroselerotic plaques were examined by histopathology with HE or Masson＇s trichrome staining. Immunohistocbemical staining was used to detect the expression of BrdU in the plaques, and hsC-RP, MMP-9 and PAI-1 in plasma were assayed at 3 days and 4 weeks after mobilization, respectively. Results At 4 weeks after mobilization, more endothelial cells and collagen fibers were found in the disrupted plaques in the mobilization group. Immunohistochemical staining revealed that there were BrdU positive cells in the plaques in the mobilization group. The expression of MMP-9, hs-CRP and PAl-1 in the mobilization group decreased significantly at 4 weeks after mobilization. Conclusion Mobilization of bone marrow stem cells shows stabilizing and repairing effects on thedisrupted atherosclerotic plaques by increasing endothelial ceils and collagen fibers, and decreasing the expression of MMP-9,hs-CRP and PAI-I significantly.