Tyml K, Mathieu-Costello O, Cheng L, Noble E G
A. C. Burton Vascular Biology Laboratory, London Health Sciences Research, and Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada N6A 5C1.
J Appl Physiol (1985). 1999 Oct;87(4):1496-505. doi: 10.1152/jappl.1999.87.4.1496.
The aim of the study was to address discrepant findings in the literature regarding coupling between decreased functional demand during disuse and reduced capillarity. We previously reported [K. Tyml, O. Mathieu-Costello, and E. Noble. Microvasc. Res. 49: 17-32, 1995] that severe disuse of rat extensor digitorum longus (EDL) muscle caused by a 2-wk application of tetrodotoxin (TTX) on the sciatic nerve is not accompanied by capillary loss. Using the same animal model, the present study examined whether this absence of coupling could be explained in terms of 1) too short a duration of disuse and 2) muscle-specific response to disuse. Fischer 344 rats were exposed to either no treatment (control) or to 2- or 8-wk TTX applications. Fiber size, capillary density per fiber cross-sectional area, and capillary-to-fiber (C/F) ratio were determined by morphometry in the EDL muscle (control, 2- and 8-wk groups) and in the superficial portion of medial gastrocnemius (Gas) muscle (control, 2 wk). In both muscles, microvascular blood flow was evaluated by intravital microscopy [red blood cell velocity in capillaries (V(RBC))] and by laser Doppler flowmetry (LDF). Regardless of duration of TTX application or muscle type, TTX-induced disuse resulted in a significant reduction of fiber area (44-71%). However, capillary density increased in EDL muscle (both at 2 and 8 wk) but not in Gas muscle. C/F ratio decreased in EDL muscle at 8 wk (18%) and in Gas muscle (39%). This indicates that the effect on capillarity depended on duration of disuse and on muscle type. V(RBC) and LDF signal were significantly larger in EDL than in Gas muscle. Analysis of change in capillarity vs. V(RBC) suggested that the outcome of disuse may be modulated by blood flow. We conclude that the duration of skeletal muscle disuse per se does not dictate capillary loss, and we hypothesize that discrepant findings of coupling between functional demand and capillarity could be due to the presence/absence of flow-related angiogenesis superimposed on the capillary removal process during disuse.
本研究的目的是解决文献中关于废用期间功能需求降低与毛细血管减少之间耦合关系的不一致发现。我们之前报道过[K. Tyml, O. Mathieu-Costello, and E. Noble. Microvasc. Res. 49: 17 - 32, 1995]，通过对坐骨神经应用2周的河豚毒素（TTX）导致大鼠趾长伸肌（EDL）严重废用，并未伴随毛细血管丢失。利用相同的动物模型，本研究探讨了这种耦合关系缺失是否可以从以下两方面来解释：1）废用持续时间过短；2）肌肉对废用的特异性反应。将Fischer 344大鼠分为未处理组（对照组）以及接受2周或8周TTX处理的组。通过形态计量学测定EDL肌肉（对照组、2周组和8周组）以及腓肠肌内侧浅层（Gas）肌肉（对照组、2周组）的纤维大小、每纤维横截面积的毛细血管密度以及毛细血管与纤维（C/F）比值。在这两种肌肉中，通过活体显微镜检查[毛细血管内红细胞速度（V(RBC)）]和激光多普勒血流仪（LDF）评估微血管血流。无论TTX应用的持续时间或肌肉类型如何，TTX诱导的废用均导致纤维面积显著减小（44 - 71%）。然而，EDL肌肉中的毛细血管密度增加（2周和8周时均增加），而Gas肌肉中的毛细血管密度未增加。8周时EDL肌肉中的C/F比值降低（18%），Gas肌肉中的C/F比值降低（39%）。这表明对毛细血管的影响取决于废用持续时间和肌肉类型。EDL肌肉中的V(RBC)和LDF信号显著大于Gas肌肉中的信号。毛细血管变化与V(RBC)的分析表明，废用的结果可能受血流调节。我们得出结论，骨骼肌废用本身并不决定毛细血管丢失，并且我们推测功能需求与毛细血管之间耦合关系的不一致发现可能是由于在废用期间毛细血管清除过程中叠加了与血流相关的血管生成的存在与否。
