摘要：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

GAO Xiulin ,Ding Hu ,Joel D. Kopple

(Division of Nephrology,Fuxing Hospital Capital University of Medical Sciences,Beijing 100038,China)

Abstract：Objective To explore the actions of insulin-like growth factor-1 (IGF-1) on protein metabolism in skeletal muscle of rats with chronic renal failure.Methods The IGF-1 levels in serum and skeletal muscle of rats with CRF and sham operation (SO),pair-fed controls were measured bv radio immunoassav (RIA).Total tvrosine in the supernatant from the medium was measured fluorometrically.Basal protein synthesis rate and degradation rate in skeletal muscle were calculated using measurements of radiolabeled tyrosine uptake and total tyrosine release frum skeletal muscle.The effects of recombinant human insulin-like growth factor-1 (rhIGF-1) on muscle protein synthesis and degradation were evaluated in animals.Results IGF-1 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 basal 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 basal 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-1 showed that the enhancement in muscle protein synthesis induced by increasing concentrations of rhIGF-1 (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-1 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-1 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.

Keywords：Insulin-like growth factor-1;Renal failure,chronic;Skeletal muscle;Protein参考文献：

［1］Kopple JD.Effect of nutrition on morbidity and mortality in maintenance dialysis patients.Am J Kidney Dis,1994,24:1002-1009.

［2］Ahonen RE.Light microscopic study of striated muscle in uremia.Acta Neuropathol,1980,49:51-55

［3］卢方平.胰岛素样生长因子-1与慢性肾衰患者的营养状况.中华肾脏病杂志,1998,14:62-64.

［4］袁群英,陈伟英,李惠群,等.胰岛素样生长因子-1与腹膜透析患者营养状况.中华肾脏病杂志,1999,15:354-357.

［5］Schulman G,Wingard RL,Hutehison RL,et al.The effects of recombinant human growth hormone and intradialytic parenteral nutrition in malnourished hemodialysis patients.Am J Kidney Dis,1993,21:527-534.

［6］Peng S,Fouque D,Kopple JD,Insulin-like growth factor 1(IGF-1)causes anabolism in malnourished CAPD patients.J Am Soc Nephrol,1993,4:414.

［7］Eouque D,Peng S,Kopple JD,Impaired metabolic response to recombinant insulin-like growth factor-1 in dialysis patients,Kidney Int,1995,47:876-883.

［8］Ding H,Gao XL,Hirschberg R,et al.Impaired actions of insulin-like growth factor 1 on protein synthesis and degradation in skeletal muscle of rats with chronic renal failure,evidence for a postreceptor defect.J Clin Invest,1996,97:1064-1075.

［9］Clark AS,Mitch WE,Comparison of protein synthesis and degradation in incubated and perfused muscle.Bioehem J,1983,212:649-653.

［10］Waalkes TP,Udenfriend S,A fluorometric method for the estimation of tyrosine in plasma ami tissues.J Lab Clin Med,1957,50:733-736.

［11］Rinderknecht E.Humbel RE.The amino acid sequence of human insulin-like growth factor 1 and its structural homology with proinsulin.J Biol Chem,1978,253:2769-2776.

［12］Gluckman PD,Douglas RG,Ambler GR,et al.The endocrine role of insulin-like growth faetor 1.Acta Pediatr Scand,1991,372 Suppl:97-105.

［13］Dohm GL,Elton CW,Raju MS,et al.IGF-1 stimulated glucose transport in human skeletal muscle and IGF-1 resistance in obesity and NIDDM.Diabetes,1990,39:1028-1032.

［14］Thissen JP,Ketelslegers JM,Underwood LE.Nutritional regulation of the insulin-like growth factors.Endocrinol Rev,1994,15:80-101.

［15］Chlla A,Chan W,Krieg RJ,et al.Effect of metabolic aeidosis on the expression of insulin-like growth factor and growth hormone receptor.Kidney Int,1993,44:1224-1227.

收稿日期：2000-02-20