胰岛素样生长因子1对慢性肾功能衰竭大鼠骨骼肌蛋白质代谢的影响

目的 探讨胰岛素样生长因子1（IGF-1）在慢性肾功能衰竭（CRF）大鼠骨骼肌蛋白质代谢上的作用。方法 用放射免疫分析法测定CRF大鼠和配对喂养的假手术（SO）对照大鼠血清及骨骼肌中IGF-1的含量：计算骨骼肌蛋白质的基础合成率及分解率；评估重组人胰岛素样生长因子-1（rhIGF-1）对骨骼肌蛋白质合成与分解的影响。结果（1）CRF组血清和骨骼肌中IGF-1含量明显低于SO组；（2）CRF组骨骼肌基础蛋白合成率显著低于SO组，基础蛋白分解率显著高于SO组；（3）rhIGF-1对CRF大鼠骨骼肌蛋白质合成的促进作用仅为SO大鼠的25%～44%，对其分解的抑制作用仅为SO大鼠的15%～42%。结论CRF时，血清及骨骼肌的IGF-1含量的减少和骨骼肌对IGF-1促进蛋白质合成代谢作用的抵抗可能是白质合成减少、分解增强，导致营养不良、肌肉萎缩的主要原因。

The effects of insulin-like growth factor-1 on protein metabolism in skeletal muscle of rats with chronic renal failure

Objective To explore the actions of insulin-like growth factor-l (IGF-1) on protein metabolism in skeletal muscle of rats with chronic renal failure. Methods The IGF-l levels in serum and skeletal muscle of rats with CRF and sham operation (SO), pair-fed controls were measured by radio immunoassay (RIA). Total tyrosine in the supernatant from the medium was measured fluorometrically. Basal protein synthesis rate and degradation rate in skeletal muscle were calculated using measurements of radiolaheled tyrosine uptake and total tyrosine release from skeletal muscle. The effects of recombinant human insulin-like growth factor-l (rhIGF-l ) on muscle protein synthesis and degradation were evaluated in animals. Results IGF-l levels in serum and skeletal muscle in the CRF rats were significantly lower than that in SO rats, P < 0. 001 for each comparison. The hasal protein synthesis rate in muscle of the CRF rats was significantly lower, by 22%, than that of SO rats, P < 0. 01. In contrast, the hasal protein degradation rate in the muscle of the CRF rats was increased by 78% in comparison to SO rats, P < 0. 01. Dose response curves of rhIGF-l showed that the enhancement in muscle protein synthesis induced by increasing concentrations of rhIGF-l (ranging from 25 to 500 ng/ml) in CRF rats was only 25% to 44% of that in SO rats. Similarly, the suppressive effects of the various concentrations of rhIGF-1 on protein degradation in muscle from CRF rats were only 15% to 42% of those found in SO rats. These data indicate that the effects of rhIGF-l on muscle protein turnover in CRF rats were markedly attenuated as compared to their SO pair-fed controls. Conclusions The decreased IGF-1 levels in serum and in skeletal muscle, the resistance to the anabolic effects of IGF-l on protein metabolism may be the main causes of reduced protein synthesis and enhanced protein degradation in muscle, muscle atrophy and malnutrition in patients with CRF.