Dedkov E I, Kostrominova T Y, Borisov A B, Carlson B M
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Microvasc Res. 2002 Jan;63(1):96-114. doi: 10.1006/mvre.2001.2372.
In denervated skeletal muscles, atrophy of muscle fibers and interstitial fibrosis are associated with alterations within the vascular bed. Our study has placed particular emphasis on changes occurring in resistance vessels and the microcirculatory bed of rat hindlimb skeletal muscles that had been denervated for 25 months. We found that the tunica media of the majority of long-term denervated resistance vessels undergoes deterioration. In small intramuscular arteries and arterioles, atrophic vascular smooth muscle cells (vSMCs) enclosed in a thick basal lamina are separated by expanded extracellular space. The remodeling and sclerotic changes in the arterial wall occasionally result in deformation of the lumen. It was also found that the microcirculatory bed undergoes significant alterations. In 25-month denervated extensor digitorum longus muscle, the capillary-to-fiber ratio is only 0.13 +/- 0.01 and the mean number of capillaries per fascicle decreases almost ninefold compared to contralateral control muscle. Ultrastructural findings demonstrate that 24.67 +/- 0.48% of capillaries examined in the chronically denervated fascicles show structural features typical for capillary regeneration. In addition, long cytoplasmic extensions of pericytes might develop a layer completely encircling the capillary endothelium. In pre- and postcapillary segments of the microcirculatory bed, some perivascular cells possess a phenotype that is intermediate between that of pericytes and atrophic vSMCs. RT-PCR and/or Western blot analyses showed that molecules participating in angiogenesis are detected in 25-month denervated skeletal muscle. We hypothesize that despite the fact that the microcirculatory bed of chronically denervated muscle undergoes significant reduction it still sustains the capacity for reparative capillary growth.
在失神经支配的骨骼肌中，肌纤维萎缩和间质纤维化与血管床的改变有关。我们的研究特别关注了大鼠后肢骨骼肌失神经支配25个月后阻力血管和微循环床所发生的变化。我们发现，大多数长期失神经支配的阻力血管的中膜会发生退化。在小的肌内动脉和小动脉中，被厚基膜包裹的萎缩血管平滑肌细胞（vSMC）被扩大的细胞外间隙分隔开。动脉壁的重塑和硬化变化偶尔会导致管腔变形。还发现微循环床发生了显著改变。在失神经支配25个月的趾长伸肌中，毛细血管与纤维的比例仅为0.13±0.01，每束的平均毛细血管数量与对侧对照肌肉相比几乎减少了九倍。超微结构研究结果表明，在慢性失神经支配的肌束中检查的毛细血管中有24.67±0.48%显示出典型的毛细血管再生结构特征。此外，周细胞的长细胞质延伸可能会形成一层完全包围毛细血管内皮的结构。在微循环床的毛细血管前和后段，一些血管周围细胞具有介于周细胞和萎缩性vSMC之间的表型。逆转录聚合酶链反应（RT-PCR）和/或蛋白质印迹分析表明，在失神经支配25个月的骨骼肌中可检测到参与血管生成的分子。我们推测，尽管慢性失神经支配肌肉的微循环床显著减少，但它仍保留着修复性毛细血管生长的能力。
