Zheng Yu, Xiao Mingyue, Li Ling, Li Jianan, Reinhardt Jan D, Lu Xiao
Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Institute for Disaster Management and Reconstruction, Sichuan University - Hong Kong Polytechnic University, Chengdu, Sichuan, China.
Cardiovasc Ther. 2017 Jun;35(3). doi: 10.1111/1755-5922.12257.
This study was designed to explore the mechanism of physiological ischemic training (PIT) on remote limbs, with a special focus on the potential role of endothelial progenitor cells (EPCs), vascular endothelial growth factor (VEGF), and nitric oxide (NO) in local ischemic myocardium.
Myocardial ischemia (MI) rabbit models were randomly assigned to sham-operated group (SO), training-only group (TO), MI group, PIT group, VEGF inhibitor group (VEGF-), NO inhibitor group (NO-), VEGF and NO inhibitor group (VEGF-/NO-), and EPC inhibitor group (EPC-). A constrictor was implanted around the left ventricular branch to induce controlled MI. The PIT procedure consisted of three cycles of a 3-minutes cuff inflation on the hindlimbs with a reperfusion of 5 minutes. Plasma and myocardial EPC numbers, VEGF level, and NO concentration, as well as capillary density (CD), coronary blood flow (CBF), and coronary collateral blood flow (CCBF) in myocardium, were measured.
Nonparametric statistical techniques were applied to identify the differences between groups, and regression models were used to detect correlations between agents. VEGF levels, NO concentrations, and also EPC counts in both plasma and myocardium were highest in the PIT group. Capillary density, CCBF, and CCBF/CBF were also statistically elevated in the PIT group. VEGF explained 74% of variance in NO. NO explained 65% of variance in EPCs. EPCs explained 68% of variance in capillary density. Capillary density explained 78% of variance in CCBF and CCBF/CBF.
PIT mobilized EPCs and promoted revascularization through upregulating VEGF and NO level.
本研究旨在探讨生理性缺血训练（PIT）对远隔肢体的作用机制，特别关注内皮祖细胞（EPCs）、血管内皮生长因子（VEGF）和一氧化氮（NO）在局部缺血心肌中的潜在作用。
将心肌缺血（MI）兔模型随机分为假手术组（SO）、单纯训练组（TO）、MI组、PIT组、VEGF抑制剂组（VEGF-）、NO抑制剂组（NO-）、VEGF和NO抑制剂组（VEGF-/NO-）以及EPC抑制剂组（EPC-）。在左心室分支周围植入缩窄器以诱导可控性MI。PIT程序包括在后肢进行3个周期的3分钟袖带充气，随后再灌注5分钟。测量血浆和心肌中的EPC数量、VEGF水平、NO浓度，以及心肌中的毛细血管密度（CD）、冠状动脉血流量（CBF）和冠状动脉侧支血流量（CCBF）。
应用非参数统计技术确定组间差异，并使用回归模型检测各因素之间的相关性。PIT组的VEGF水平、NO浓度以及血浆和心肌中的EPC计数均最高。PIT组的毛细血管密度、CCBF和CCBF/CBF在统计学上也有所升高。VEGF解释了NO中74%的变异。NO解释了EPCs中65%的变异。EPCs解释了毛细血管密度中68%的变异。毛细血管密度解释了CCBF和CCBF/CBF中78%的变异。
PIT通过上调VEGF和NO水平来动员EPCs并促进血管再生。
