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基质细胞衍生因子联合骨髓单个核细胞移植治疗大鼠肢体缺血的实验研究

SDF-1 combined with bone marrow mononuclear cell transplantation for the treatment of hindlimb ischemia in rats
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摘要 目的将基质细胞衍生因子(SDF-1)用于自体骨髓单个核细胞(BM-MNC)移植治疗肢体缺血,初步探讨SDF-1促进血管新生的机理和疗效。方法建立大鼠左后肢缺血模型,将动物随机分为非缺血对照组,缺血对照组,SDF-1局部应用组,自体BM-MNC移植组以及两者联合应用组。检测缺血后24 h左后肢腓肠肌SDF-1含量及CD133+细胞数量;于移植后4周动脉造影后处死动物,免疫组化法检测缺血区新生血管密度,评价血管新生情况。结果缺血对照组24 h肌组织SDF-1含量为(1.31±0.20)ng/50μg总蛋白,非缺血对照组为(0.93±0.29)ng/50μg总蛋白(P<0.05); CD133+细胞数(2.10±0.62)vs.(0.24±0.10)个/HP,P<0.01。SDF-1局部应用可增加缺血区CD133+细胞浸润数量(3.64±0.69)个/HP(P<0.01);并可提高四周后组织内新生血管数量;SDF-1与自体骨髓单个核细胞移植联合应用,可进一步提高新生血管数量。结论SDF-1可能在肢体缺血后自体干细胞的动员中起重要作用,其局部应用可促进缺血区血管新生或进一步提高干细胞移植治疗缺血的疗效。 Objective To explore the mechanism and effect of stromal cell-derived factor-1 ( SDF- 1 ) local application in combination with transplantation of autologous bone marrow mononuclear cells ( BM- MNCs) for the treatment of rat hindlimb ischemia. Methods Left hindlimb ischemia model was established in Wistar rats, which was divided into five groups randomly: Nonischemic control, Ischemic control, SDF-1 local application group, BM-MNC transplantation group, and A combination of SDF-1 and BM-MNC group. Local SDF-1 and CD133 ^+ cells in the ischemic region were detected 24 h after ischemia. After 4 weeks the intensity of neovasculorization were evaluated by means of DSA and immunohistochemistry before the rats were sacrificed. Results In contrast to nonischemic control, SDF-1 significantly increased in ischemic muscles in 24 hours, ( 1.31 ± 0. 20) ng/50 μg total protein vs (0. 93 ± 0. 29) ng/50 μg total protein(P〈0.05). CD133^+ cells significantly increased, (2. 10 ±0.62) vs. (0.24 ±0. 10)/HP(P 〈 0. 01 ). Intramuscularly local administration of SDF-1 yielded a higher increase of CD133^+ cells, ( 3.64 ± 0. 69)/HP(P 〈0. 01 ). The density of capillaries after 4 weeks was much greater in this group than that of ischemic control. Conclusion SDF-1 may play an important role in case of limb ischemia mobilizing autologous stem cells to ischemic region. Local application of SDF-1 enhances angiogenesis in combination with autologous BM-MNC transplantation.
出处 《中华普通外科杂志》 CSCD 北大核心 2006年第7期526-529,共4页 Chinese Journal of General Surgery
基金 黑龙江省科技攻关基金资助项目GC05C40703 哈尔滨医科大学附属第二医院青年基金资助项目(2005-13)
关键词 细胞因子类 干细胞 缺血 四肢 动物实验 Cytokines Stem cells Ischemia Extremities Animal experimentation
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参考文献8

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