Faculty of Medicine, Department of Physiology, Complutense University of Madrid, Madrid, Spain.
Am J Physiol Regul Integr Comp Physiol. 2010 Aug;299(2):R541-51. doi: 10.1152/ajpregu.00211.2010. Epub 2010 Jun 2.
Adjuvant arthritis is an animal model of rheumatoid arthritis that decreases liver and circulating IGF-I as well as skeletal muscle mass. The aim of this work was to elucidate whether IGF-I administration was able to prevent the effect of arthritis on body weight and on two skeletal muscles, gastrocnemius and soleus. On day 4 after adjuvant injection, control and arthritic rats were treated with IGF-I (100 microg/kg s.c.) two times a day, until day 15 when all rats were killed. Arthritis decreased body weight gain and gastrocnemius weight. In arthritic rats, IGF-I treatment increased body weight gain and gastrocnemius weight, without modifying food intake or the external signs of arthritis. Arthritis increased atrogin-1 and muscle ring finger 1 (MuRF1) gene expression in the gastrocnemius and to a lesser extent in the soleus muscle. IGF-I attenuated the arthritis-induced increase in atrogin-1 and MuRF1 expression in the gastrocnemius, whereas it did not modify the expression of these genes in the soleus muscle. Arthritis also increased IGF-binding protein (IGBP)-3 and IGFBP-5 gene expression in gastrocnemius and soleus, whereas IGF-I administration decreased IGFBP-3, but not IGFBP-5, gene expression in both muscles. In both groups of arthritic rats and in control rats treated with IGF-I, proliferating cell nuclear antigen and myogenic differentiation proteins were increased in the gastrocnemius. These data suggest that the inhibitory effect of chronic arthritis on skeletal muscle is higher in fast glycolytic than in slow oxidative muscle and that IGF-I administration attenuates this effect and decreases atrogin-1 and IGFBP-3 gene expression.
佐剂性关节炎是一种类风湿关节炎的动物模型，它会降低肝脏和循环中的 IGF-I 以及骨骼肌质量。本研究的目的是阐明 IGF-I 给药是否能够预防关节炎对体重和两种骨骼肌（比目鱼肌和跖肌）的影响。在佐剂注射后第 4 天，对照组和关节炎组大鼠每天两次接受 IGF-I（100μg/kg sc）治疗，直至第 15 天所有大鼠被处死。关节炎降低了体重增加和比目鱼肌的重量。在关节炎大鼠中，IGF-I 治疗增加了体重增加和比目鱼肌的重量，而不改变食物摄入量或关节炎的外在迹象。关节炎增加了比目鱼肌和跖肌中 atrogin-1 和肌肉环指 1（MuRF1）基因的表达，而在跖肌中则表达较少。IGF-I 减弱了关节炎引起的比目鱼肌中 atrogin-1 和 MuRF1 表达的增加，而对跖肌中这些基因的表达没有影响。关节炎还增加了比目鱼肌和跖肌中 IGF 结合蛋白（IGBP）-3 和 IGBP-5 基因的表达，而 IGF-I 给药降低了这两种肌肉中 IGBP-3，但不降低 IGBP-5，的基因表达。在两组关节炎大鼠和接受 IGF-I 治疗的对照组大鼠中，比目鱼肌中增殖细胞核抗原和肌源性分化蛋白增加。这些数据表明，慢性关节炎对骨骼肌的抑制作用在快速糖酵解肌中高于慢速氧化肌，IGF-I 给药减弱了这种作用，并降低了 atrogin-1 和 IGBP-3 基因的表达。
