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通过生理性缺血训练增强内皮祖细胞向缺血心肌的归巢能力。

Enhancement of homing capability of endothelial progenitor cells to ischaemic myocardium through physiological ischaemia training.

机构信息

Wuxi No.2 Hospital, affiliated with Nanjing Medical University, Nanjing, China.

出版信息

J Rehabil Med. 2011 May;43(6):550-5. doi: 10.2340/16501977-0815.

DOI:10.2340/16501977-0815
PMID:21533336
Abstract

OBJECTIVE

To investigate the effects of physiological ischaemia training on the quantity and activity of endothelial progenitor cells in rabbits with intermittent myocardial ischaemia.

METHODS

A reversible coronary artery water balloon occluder (5.0 mm inner diameter) was placed around the proximal left ventricular branch and intermittent myocardial ischaemia was induced by deflation and inflation of the occluder. A wire electrode was inserted longitudinally into the epineurium of the sciatic nerve to generate physiological ischaemia training through isometric contraction induced by electrical stimulation. Rabbits were randomly divided into 3 groups: a sham operated group (SO), an intermittent myocardial ischaemia-only group (MI), and an MI plus physiological ischaemia training group (PT). Intermittent myocardial ischaemia was induced with 2-min ischaemia followed by 1-h reperfusion. Physiological ischaemia training was induced by electrical stimulation (40% maximum current strength, 1 ms, 40 Hz), 4-min per session, twice a day, 5 days per week for 4 weeks. At the end-points, endothelial progenitor cells were isolated and cultured for analysis of their migration ability. Endothelial progenitor cells were identified by dual-staining with Dil-labelled acetylated low-density lipoprotein and fluorescein isothiocyanate-labelled Ulex europaeus agglutinin-1. Circulating endothelial progenitor cells (CD34(+)/Flk-1(+)) were counted by fluorescence-activated cell sorter, and capillary density was evaluated by immunohistochemistry examination.

RESULTS

Group PT showed the highest migration capacity of endothelial progenitor cells (151 cells, standard deviation 16/high power field) and the highest increase in circulating endothelial progenitor cells (p < 0.01) after 4 weeks' physiological ischaemia training. Capillary density in the myocardium was also significantly enhanced in group PT (p < 0.05). Pearson's analysis demonstrated a positive correlation between the number circulating endothelial progenitor cells and capillary density in the myocardium after 4 weeks' physiological ischaemia training (p < 0.05).

CONCLUSION

Physiological ischaemia training may enhance the quantity and activity of endothelial progenitor cells in the blood, resulting in an increase in angiogenesis in the ischaemic heart region.

摘要

目的

研究生理性缺血训练对兔间歇性心肌缺血时内皮祖细胞数量和活性的影响。

方法

采用可调节冠状动脉水球囊阻塞器(内径 5.0mm)环绕左心室近端分支,通过球囊放气和充气诱导间歇性心肌缺血。将一根金属丝电极纵向插入坐骨神经的神经外膜,通过电刺激引起等长收缩,进行生理性缺血训练。将兔子随机分为 3 组:假手术组(SO)、单纯间歇性心肌缺血组(MI)和 MI 加生理性缺血训练组(PT)。间歇性心肌缺血采用 2min 缺血,随后 1h 再灌注。生理性缺血训练采用电刺激(40%最大电流强度、1ms、40Hz),每次 4min,每天 2 次,每周 5 天,共 4 周。在终点,分离和培养内皮祖细胞,分析其迁移能力。用 Dil 标记的乙酰化低密度脂蛋白和异硫氰酸荧光素标记的荆豆凝集素-1双重染色鉴定内皮祖细胞。用流式细胞术计数循环内皮祖细胞(CD34(+)/Flk-1(+)),并用免疫组织化学法检测毛细血管密度。

结果

PT 组在 4 周生理性缺血训练后,内皮祖细胞的迁移能力最强(151 个细胞,标准差 16/高倍视野),循环内皮祖细胞增加最多(p<0.01)。PT 组心肌毛细血管密度也明显增加(p<0.05)。Pearson 分析表明,4 周生理性缺血训练后循环内皮祖细胞数量与心肌毛细血管密度呈正相关(p<0.05)。

结论

生理性缺血训练可增强血液中内皮祖细胞的数量和活性,增加缺血心肌区域的血管生成。

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