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缺血预处理在实验性肢体缺血危象中的血管生成作用。

The angiogenic effects of ischemic conditioning in experimental critical limb ischemia.

机构信息

Department of Surgery, Etlik İhtisas Training and Research Hospital, Ankara, Turkey.

Division of Vascular Surgery, Department of General Surgery, Ankara University, Faculty of Medicine, Ankara, Turkey.

出版信息

Eur J Vasc Endovasc Surg. 2014 Feb;47(2):172-9. doi: 10.1016/j.ejvs.2013.11.001. Epub 2013 Nov 11.

DOI:10.1016/j.ejvs.2013.11.001
PMID:24333045
Abstract

OBJECTIVES

Ischemic conditioning (IC) is a method of angiogenic stimulus for limb ischemia. Here, we aimed to investigate the effects of short-term repeated ischemic stimulus on critical lower limb ischemic injury.

METHODS

Rats were divided into four groups consisting of 40 animals in each group: sham, ischemia, local IC, and remote IC groups. Right-leg critical limb ischemia was achieved through ligation of the iliac artery and vein in male Sprague-Dawley rats except the sham group. Repeated transient ischemia using the tourniquet method was used for IC of lower extremities in the local and remote groups. IC was performed on the right leg for the local group and on the left leg for the remote group. Ten rats in each group were sacrificed for evaluation on days 1, 7, 14, and 30. Endothelial progenitor cell (EPC) counts were measured. Gastrocnemius muscles were evaluated for the degree of ischemia. Laser Doppler blood flow measurements were performed in order to make comparison between the blood flows of the limbs of the groups.

RESULTS

The blood flow in the right limb of rats in the sham (1.65 perfusion units [PU]) and local IC (1.67 PU) groups was significantly higher than the ischemic group (1.17 PU) (p = .001 and p = .022 respectively). The levels of EPCs in the ischemia (1.09 ± 0.5) and remote IC groups (1.36 ± 0.8) were significantly higher than the sham (0.38 ± 0.2) group on day 7 (p = .026 and p = .002 respectively). Remote IC and local IC groups exhibited increased histopathological ischemia on day 7 when compared with sham group (p = .001, p = .01 respectively). The angiogenic scores on the 7th, 14th and 30th days for local IC and remote IC groups were significantly higher than sham and ischemia groups.

CONCLUSIONS

IC seems to be the potent activator of angiogenesis in ischemic tissue. This study provides preliminary data showing that repeated short ischemic stimuli may reduce critical ischemic injury by promoting angiogenesis.

摘要

目的

缺血预处理(IC)是一种促进肢体缺血血管生成的刺激方法。本研究旨在探讨短期重复缺血刺激对严重下肢缺血损伤的影响。

方法

雄性 Sprague-Dawley 大鼠除假手术组外,通过结扎髂动脉和静脉建立右下肢严重肢体缺血模型。使用止血带法对下肢进行重复短暂缺血,用于局部和远程 IC 组的 IC。局部组在右腿进行 IC,远程组在左腿进行 IC。每组 10 只大鼠于第 1、7、14 和 30 天处死,评估内皮祖细胞(EPC)计数。评估腓肠肌缺血程度。进行激光多普勒血流测量,比较各组肢体血流。

结果

假手术(1.65 灌注单位 [PU])和局部 IC(1.67 PU)组大鼠右肢血流明显高于缺血组(1.17 PU)(p =.001 和 p =.022)。缺血(1.09 ± 0.5)和远程 IC 组(1.36 ± 0.8)EPC 水平在第 7 天明显高于假手术组(p =.026 和 p =.002)。与假手术组相比,远程 IC 和局部 IC 组在第 7 天表现出组织学缺血程度增加(p =.001,p =.01)。第 7、14 和 30 天局部 IC 和远程 IC 组的血管生成评分明显高于假手术和缺血组。

结论

IC 似乎是缺血组织中血管生成的有效激活剂。本研究提供了初步数据,表明重复短暂的缺血刺激可能通过促进血管生成来减轻严重缺血损伤。

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