Benefit of combined extracorporeal shock wave and bone marrow-derived endothelial progenitor cells in protection against critical limb ischemia in rats
Benefit of combined extracorporeal shock wave and bone marrow-derived endothelial progenitor cells in protection against critical limb ischemia in rats
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DOI：
10.1097/ccm.0b013e31822d74d0
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发表时间：
2012-01-01
影响因子：
8.8
通讯作者：
Yip, Hon-Kan
中科院分区：
文献类型：
--
作者：
Yeh, Kuo-Ho;Sheu, Jiunn-Jye;Yip, Hon-Kan
目的：我们假设体外冲击波和骨髓内皮祖细胞联合治疗可能对大鼠重度肢体缺血有增强的保护作用。方法:雄性Sprague-Dawley大鼠（每组激光多普勒研究n = 9，实验室检查n = 6）分为1组（假性对照）、2组（培养基处理危重肢体缺血）、3组（肌内骨髓内皮祖细胞[2.0 × 10(6)个细胞]处理危重肢体缺血）、4组（体外冲击波[280次脉冲，0.1 mJ/mm(2)]处理危重肢体缺血）。5组（联合骨髓源性内皮祖细胞体外冲击波组）急性肢体缺血诱导。结果：第21天，激光多普勒显示，与其他各组相比，2组缺血血流/正常血流之比明显降低（p < 0.001）。5组线粒体细胞色素c、基质细胞源性因子-1、c - x - c趋化因子受体4型、血管内皮生长因子和内皮型一氧化氮合酶蛋白表达量显著高于2 ~ 4组，3、4组显著高于2组（均p < 0.01）。与2 ~ 4组相比，5组促炎和凋亡生物标志物信使RNA及氧化应激表达降低，且3、4组显著低于2组（均p < 0.01）。抗炎和抗凋亡生物标志物信使RNA表达在2组低于其他组（均p < 0.01）。免疫荧光染色显示，5组缺血区CD31+基质细胞源性因子-1+、趋化因子受体4+、血管性血变因子+细胞及血管数量高于2 ~ 4组，3、4组高于2组（均p < .04）。结论：骨髓内皮祖细胞联合体外冲击波治疗对改善危重肢体缺血的作用优于骨髓内皮祖细胞或体外冲击波单独治疗。（Crit Care Med 2012; 40:169-177）
Objectives: We hypothesized that combined treatment with extracorporeal shock wave and bone marrow-derived endothelial progenitor cells might exert enhanced protection against critical limb ischemia in rats.Methods: Male Sprague-Dawley rats (n = 9 for laser Doppler study and n = 6 for laboratory examinations in each group) were divided into group 1 (sham control), group 2 (critical limb ischemia treated with culture medium), group 3 (critical limb ischemia treated with intramuscular bone marrow-derived endothelial progenitor cells [2.0 x 10(6) cells]), group 4 (critical limb ischemia treated with extracorporeal shock wave [280 impulses at 0.1 mJ/mm(2)]), and group 5 (combined bone marrow-derived endothelial progenitor cell-extracorporeal shock wave) after critical limb ischemia induction.Results: By day 21, laser Doppler showed substantially lower ratios of ischemic/normal blood flow in group 2 compared with other groups (p < .001). The protein expressions of mitochondrial cytochrome c, stromal cell-derived factor-1, C-X-C chemokine receptor type 4, vascular endothelial growth factor, and endothelial nitric oxide synthase were remarkably higher in group 5 than in groups 2 to 4, and notably higher in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of proinflammatory and apoptotic biomarkers and oxidative stress were reduced in group 5 compared with groups 2 to 4, and notably lower in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of anti-inflammatory and antiapoptotic biomarkers were lower in group 2 than in other groups (all p < .01). Immunofluorescent staining showed higher numbers of CD31+ stromal cell-derived factor-1+, chemokine receptor type 4+, and von Willebrand factor+ cells, and vessels in the ischemic area in group 5 than in groups 2 to 4, and in groups 3 and 4 than in group 2 (all p < .04).Conclusion: Combined treatment with bone marrow-derived endothelial progenitor cells and extracorporeal shock wave is superior to either bone marrow-derived endothelial progenitor cells or extracorporeal shock wave alone in improving ischemia in rodent critical limb ischemia. (Crit Care Med 2012; 40:169-177)