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移植内皮祖细胞治疗高血糖兔后肢缺血的促血管生成疗效

Pro-angiogenic efficacy of transplanting endothelial progenitor cells for treating hindlimb ischemia in hyperglycemic rabbits.

作者信息

Yu Ping, Li Qiang, Liu Ying, Zhang Jinchao, Seldeen Ken, Pang Manhui

机构信息

Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

出版信息

J Diabetes Complications. 2015 Jan-Feb;29(1):13-9. doi: 10.1016/j.jdiacomp.2014.09.003. Epub 2014 Sep 16.

DOI:10.1016/j.jdiacomp.2014.09.003
PMID:25283487
Abstract

AIMS

To evaluate the effectiveness of endothelial progenitor cells (EPCs) therapy in ischemia with or without hyperglycemia.

METHODS

Japanese White Rabbits were randomly assigned to three groups, group SH, hyperglycemia with sham therapy (n=10); group NE, normoglycemia with autologous EPCs transplantation therapy (n=12); and group HE, hyperglycemia with autologous EPCs transplantation therapy (n=12). Hyperglycemia was induced by injecting alloxan and sustained for 12weeks. Hindlimb ischemia was induced by complete excision of the femoral artery. Ex vivo-expanded EPCs were derived from autologous bone marrow and transplanted intermuscularily in the ischemic hindlimb. Fourteen days after transplantation, the indicators were determined.

RESULTS

There is no difference of the functions of ex vivo-expanded EPCs from autologous bone marrow between normoglycemic and hyperglycemic groups. We found significant improvement in both EPCs transplantation therapy groups compared to sham, in terms of the angiogenesis index (8.62±1.36, 11.12±2.23, 12.35±2.97), capillary density (7.06±0.91, 13.51±1.16, 13.90±2.78), capillary to muscle fiber ratio (0.68±0.09, 0.96±0.11,0.89±0.10), muscle VEGF expression (0.22±0.07, 0.41±0.08, 0.38±0.07ng/g). We found no significant differences between hyperglycemic and normoglycemic EPCs therapy groups except for 5 pro-angiogenic genes that were upregulated in HE as compared to NE.

CONCLUSION

Ex vivo expanded EPCs from autologous bone marrow transplantation is an effective therapeutic method for hindlimb ischemia in rabbits regardless of glycemic state.

摘要

目的

评估内皮祖细胞(EPCs)疗法在伴有或不伴有高血糖的缺血情况下的有效性。

方法

将日本白兔随机分为三组,SH组,高血糖伴假手术治疗(n = 10);NE组,正常血糖伴自体EPCs移植治疗(n = 12);HE组,高血糖伴自体EPCs移植治疗(n = 12)。通过注射四氧嘧啶诱导高血糖,并持续12周。通过完全切除股动脉诱导后肢缺血。体外扩增的EPCs来源于自体骨髓,并肌肉内移植到缺血后肢。移植后14天,测定各项指标。

结果

正常血糖组和高血糖组自体骨髓来源的体外扩增EPCs功能无差异。我们发现,与假手术组相比,两个EPCs移植治疗组在血管生成指数(8.62±1.36,11.12±2.23,12.35±2.97)、毛细血管密度(7.06±0.91,13.51±1.16,13.90±2.78)、毛细血管与肌纤维比值(0.68±0.09,0.96±0.11,0.89±0.10)、肌肉VEGF表达(0.22±0.07,0.41±0.08,0.38±0.07ng/g)方面均有显著改善。除了与NE组相比HE组有5个促血管生成基因上调外,我们发现高血糖和正常血糖EPCs治疗组之间无显著差异。

结论

自体骨髓移植体外扩增的EPCs是一种治疗兔后肢缺血的有效方法,无论血糖状态如何。

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