低分子质量内皮细胞刺激血管生成因子与低频电刺激诱导大鼠骨骼肌毛细血管生长的关系

Low-molecular-mass endothelial cell-stimulating angiogenic factor in relation to capillary growth induced in rat skeletal muscle by low-frequency electrical stimulation.

作者信息

Brown M D, Hudlicka O, Makki R F, Weiss J B

机构信息

Department of Sport and Exercise Science, University of Birmingham, UK.

出版信息

Int J Microcirc Clin Exp. 1995 May-Jun;15(3):111-6. doi: 10.1159/000178960.

DOI:10.1159/000178960

PMID:8707459

Abstract

The involvement of endothelial cell-stimulating angiogenic factor (ESAF) in capillary growth was studied in adult rat skeletal muscles (tibialis anterior, TA, and extensor digitorum longus, EDL) in which capillary growth was induced by chronic unilateral electrical stimulation (10 Hz, 8 h/day for 7 days), and in sham-operated and unoperated control muscles. ESAF was assayed by its ability to activate latent collagenase in units per hour per milligram protein. Anatomical capillary density (CD, number of capillaries per mm2) and capillary per fibre ratio (C/F) were estimated in frozen sections from the same muscles after staining for endothelial alkaline phosphatase. In control muscles, ESAF levels were inversely related to capillary supply, being highest (1.82 +/- 0.25 units) in the glycolytic cortex of TA (CD 273 +/- 18/mm2, C/F 1.26 +/- 0.07), lowest (1.04 +/- 0.02 units) in its oxidative highly capillarized core (CD 862 +/- 60/mm2, C/F 2.05 +/- 0.04), and intermediate in EDL (ESAF 1.59 +/- 0.37 units, CD 527 +/- 26/mm2, C/F 1.44 +/- 0.06). Neither capillary supply nor ESAF levels were affected by sham operation. However, chronic electrical stimulation increased capillary supply significantly in EDL (CD 61% greater than in controls, C/F 45% greater) and ESAF levels were elevated 3-fold to 4.77 +/- 0.74 units. In TA muscles, stimulation increased capillary supply specifically in the glycolytic cortex (C/F 2.51 +/- 0.09, p < 0.0001 vs. control) and ESAF levels were increased significantly in this region to 3.19 +/- 0.55 units (p < 0.05, vs. control). C/F ratio and ESAF in the oxidative core of TA (2.31 +/- 0.05 and 1.48 +/- 0.23 units, respectively) were not significantly different from control values. Thus, chronic electrical stimulation, which is known to increase both shear stress and wall tension in capillaries and induce angiogenesis, also increased ESAF activity.

摘要

在成年大鼠骨骼肌（胫前肌，TA，和趾长伸肌，EDL）中研究了内皮细胞刺激血管生成因子（ESAF）在毛细血管生长中的作用，这些骨骼肌中的毛细血管生长通过慢性单侧电刺激（10Hz，每天8小时，共7天）诱导，同时设置了假手术组和未手术的对照组肌肉。通过每毫克蛋白质每小时激活潜伏胶原酶的能力来测定ESAF。在对内皮碱性磷酸酶染色后，从相同肌肉的冰冻切片中估计解剖学毛细血管密度（CD，每平方毫米毛细血管数量）和毛细血管与肌纤维比率（C/F）。在对照肌肉中，ESAF水平与毛细血管供应呈负相关，在TA的糖酵解皮质中最高（1.82±0.25单位）（CD 273±18/mm²，C/F 1.26±0.07），在其氧化的高毛细血管化核心中最低（1.04±0.02单位）（CD 862±60/mm²，C/F 2.05±0.04），在EDL中处于中间水平（ESAF 1.59±0.37单位，CD 527±26/mm²，C/F 1.44±0.06）。假手术对毛细血管供应和ESAF水平均无影响。然而，慢性电刺激使EDL中的毛细血管供应显著增加（CD比对照组大61%，C/F大45%），ESAF水平升高至3倍，达到4.77±0.74单位。在TA肌肉中，刺激特异性地增加了糖酵解皮质中的毛细血管供应（C/F 2.51±0.09，与对照组相比p<0.0001），该区域的ESAF水平显著增加至3.19±0.55单位（与对照组相比p<0.05）。TA氧化核心中的C/F比率和ESAF（分别为2.31±0.05和1.48±0.23单位）与对照值无显著差异。因此，已知慢性电刺激会增加毛细血管中的剪切应力和壁张力并诱导血管生成，同时也增加了ESAF活性。